A 3-styrylchromone converted from trimebutine 3D pharmacophore possesses dual suppressive effects on RAGE and TLR4 signaling pathways
Biochem Biophys Res Commun. 2021 Jun 7;566:1-8. doi: 10.1016/j.bbrc.2021.05.096. Online ahead of print.ABSTRACTReceptor for advanced glycation end-products (RAGE) and Toll-like receptors (TLRs) are potential therapeutic targets in the treatment of acute and chronic inflammatory diseases. We previously reported that trimebutine, a spasmolytic drug, suppresses RAGE pro-inflammatory signaling pathway in macrophages. The aim of this study was to convert trimebutine to a new small molecule using in silico 3D pharmacophore similarity search, and dissect the mechanistic anti-inflammatory basis. Of note, a unique 3-styrylchromone ...
Source: Biochemical and Biophysical Research communications - June 10, 2021 Category: Biochemistry Authors: Miwa Okazawa Takahiro Oyama Hideaki Abe Hiroaki Yamazaki Atsushi Yoshimori Mitsutoshi Tsukimoto Kazumi Yoshizawa Koichi Takao Yoshiaki Sugita Takanori Kamiya Fumiaki Uchiumi Hiroshi Sakagami Takehiko Abe Sei-Ichi Tanuma Source Type: research

LncRNA JPX regulates proliferation and apoptosis of nucleus pulposus cells by targeting the miR-18a-5p/HIF-1 α/Hippo-YAP pathway
In conclusion, overexpression of lncRNA JPX upregulated HIF-1α by inhibiting the expression of miR-18a-5p, thereby inhibiting the Hippo-YAP pathway. By inhibiting this pathway, JPX overexpression promoted the proliferation of HNPCs and decreased their apoptosis. Therefore, the lncRNA JPX is a potential new target.PMID:34111667 | DOI:10.1016/j.bbrc.2021.05.075 (Source: Biochemical and Biophysical Research communications)
Source: Biochemical and Biophysical Research communications - June 10, 2021 Category: Biochemistry Authors: Helin Yang Guangji Wang Jian Liu Mingxia Lin Jian Chen Yehan Fang Yibo Li Wentao Cai Daolu Zhan Source Type: research

Involvement of ferroptosis in human motor neuron cell death
Biochem Biophys Res Commun. 2021 Jun 7;566:24-29. doi: 10.1016/j.bbrc.2021.05.095. Online ahead of print.ABSTRACTFerroptosis was recently defined as a novel type of programmed cell death depending on iron and lipid peroxidation. It is biologically different from other types of cell death such as apoptosis. While the involvement of ferroptosis in cancer, patient and animal model have been intensely studied, ferroptosis in human motor neuron model is still clearly unknown. Here we carefully assessed ferroptosis using human iPS cell-derived motor neuron (hiMNs). We found that almost all hiMNs died by the treatment of glutathi...
Source: Biochemical and Biophysical Research communications - June 10, 2021 Category: Biochemistry Authors: Tsuyoshi Matsuo Keiko Adachi-Tominari Osamu Sano Takayuki Kamei Masahiro Nogami Kazuhiro Ogi Hideyuki Okano Masato Yano Source Type: research

Novel HIV PR inhibitors with C4-substituted bis-THF and bis-fluoro-benzyl target the two active site mutations of highly drug resistant mutant PR < sup > S17 < /sup >
Biochem Biophys Res Commun. 2021 Jun 7;566:30-35. doi: 10.1016/j.bbrc.2021.05.094. Online ahead of print.ABSTRACTThe emergence of multidrug resistant (MDR) HIV strains severely reduces the effectiveness of antiretroviral therapy. Clinical inhibitor darunavir (1) has picomolar binding affinity for HIV-1 protease (PR), however, drug resistant variants like PRS17 show poor inhibition by 1, despite the presence of only two mutated residues in the inhibitor-binding site. Antiviral inhibitors that target MDR proteases like PRS17 would be valuable as therapeutic agents. Inhibitors 2 and 3 derived from 1 through substitutions at P...
Source: Biochemical and Biophysical Research communications - June 10, 2021 Category: Biochemistry Authors: Johnson Agniswamy Daniel W Kneller Arun K Ghosh Irene T Weber Source Type: research

miR-190a-5p regulates cardiomyocytes response to ferroptosis via directly targeting GLS2
Biochem Biophys Res Commun. 2021 Jun 7;566:9-15. doi: 10.1016/j.bbrc.2021.05.100. Online ahead of print.ABSTRACTFerroptosis is a novel identified form of regulated cell death that has been implied in the pathology of myocardial infarction (MI). However, the regulation mechanisms of ferroptosis in cardiomyocyte are still elusive. MiRNAs are a group of small non-coding RNAs that play crucial roles in various biological activities. Till now, little is known about the role of miRNA in the ferroptosis of cardiomyocytes. In the current study, we found that miR-190a-5p negatively regulate ferroptosis via directly targeting GLS2 i...
Source: Biochemical and Biophysical Research communications - June 10, 2021 Category: Biochemistry Authors: Xiaodao Zhou Mali Zhuo Yayun Zhang Erdong Shi Xujie Ma Hong Li Source Type: research

Oncogenic mutations Q61L and Q61H confer active form-like structural features to the inactive state (state 1) conformation of H-Ras protein
Biochem Biophys Res Commun. 2021 Jun 5;565:85-90. doi: 10.1016/j.bbrc.2021.05.084. Online ahead of print.ABSTRACTGTP-bound forms of Ras proteins (Ras•GTP) assume two interconverting conformations, "inactive" state 1 and "active" state 2. Our previous study on the crystal structure of the state 1 conformation of H-Ras in complex with guanosine 5'-(β, γ-imido)triphosphate (GppNHp) indicated that state 1 is stabilized by intramolecular hydrogen-bonding interactions formed by Gln61. Since Ras are constitutively activated by substitution mutations of Gln61, here we determine crystal structure...
Source: Biochemical and Biophysical Research communications - June 8, 2021 Category: Biochemistry Authors: Shigeyuki Matsumoto Haruka Taniguchi-Tamura Mitsugu Araki Takashi Kawamura Ryo Miyamoto Chiemi Tsuda Fumi Shima Takashi Kumasaka Yasushi Okuno Tohru Kataoka Source Type: research

TGF- β1 signaling is essential for tissue regeneration in the Xenopus tadpole tail
Biochem Biophys Res Commun. 2021 Jun 5;565:91-96. doi: 10.1016/j.bbrc.2021.05.082. Online ahead of print.ABSTRACTAmphibians such as Xenopus tropicalis exhibit a remarkable capacity for tissue regeneration after traumatic injury. Although transforming growth factor-β (TGF-β) receptor signaling is known to be essential for tissue regeneration in fish and amphibians, the role of TGF-β ligands in this process is not well understood. Here, we show that inhibition of TGF-β1 function prevents tail regeneration in Xenopus tropicalis tadpoles. We found that expression of tgfb1 is present before tail amputation a...
Source: Biochemical and Biophysical Research communications - June 8, 2021 Category: Biochemistry Authors: Makoto Nakamura Hitoshi Yoshida Yuka Moriyama Itsuki Kawakita Marcin Wlizla Kimiko Takebayashi-Suzuki Marko E Horb Atsushi Suzuki Source Type: research

Oncogenic mutations Q61L and Q61H confer active form-like structural features to the inactive state (state 1) conformation of H-Ras protein
Biochem Biophys Res Commun. 2021 Jun 5;565:85-90. doi: 10.1016/j.bbrc.2021.05.084. Online ahead of print.ABSTRACTGTP-bound forms of Ras proteins (Ras•GTP) assume two interconverting conformations, "inactive" state 1 and "active" state 2. Our previous study on the crystal structure of the state 1 conformation of H-Ras in complex with guanosine 5'-(β, γ-imido)triphosphate (GppNHp) indicated that state 1 is stabilized by intramolecular hydrogen-bonding interactions formed by Gln61. Since Ras are constitutively activated by substitution mutations of Gln61, here we determine crystal structure...
Source: Biochemical and Biophysical Research communications - June 8, 2021 Category: Biochemistry Authors: Shigeyuki Matsumoto Haruka Taniguchi-Tamura Mitsugu Araki Takashi Kawamura Ryo Miyamoto Chiemi Tsuda Fumi Shima Takashi Kumasaka Yasushi Okuno Tohru Kataoka Source Type: research

TGF- β1 signaling is essential for tissue regeneration in the Xenopus tadpole tail
Biochem Biophys Res Commun. 2021 Jun 5;565:91-96. doi: 10.1016/j.bbrc.2021.05.082. Online ahead of print.ABSTRACTAmphibians such as Xenopus tropicalis exhibit a remarkable capacity for tissue regeneration after traumatic injury. Although transforming growth factor-β (TGF-β) receptor signaling is known to be essential for tissue regeneration in fish and amphibians, the role of TGF-β ligands in this process is not well understood. Here, we show that inhibition of TGF-β1 function prevents tail regeneration in Xenopus tropicalis tadpoles. We found that expression of tgfb1 is present before tail amputation a...
Source: Biochemical and Biophysical Research communications - June 8, 2021 Category: Biochemistry Authors: Makoto Nakamura Hitoshi Yoshida Yuka Moriyama Itsuki Kawakita Marcin Wlizla Kimiko Takebayashi-Suzuki Marko E Horb Atsushi Suzuki Source Type: research

Structural insights into two distinct nanobodies recognizing the same epitope of green fluorescent protein
In this study, we determined the crystal structure of the nanobody Nb2 complexed with superfolder GFP (sfGFP) at a resolution of 2.2 Å. Interestingly, although the complementarity-determining regions (CDRs) of Nb2 and LaG16 sequences were only 29.7% identical, they both bound to the same epitope of GFP and existed in the same orientation. Structural analysis indicated that they achieved similar binding characteristics through different mechanisms. We further verified the kinetics and thermodynamics of binding by biolayer interferometry (BLI) and isothermal titration calorimetry (ITC). Nb2 showed a slightly higher bin...
Source: Biochemical and Biophysical Research communications - June 7, 2021 Category: Biochemistry Authors: Peiyu Zhong Ziying Wang Shihao Cheng Yiran Zhang He Jiang Rui Liu Yu Ding Source Type: research

Viral mimetic poly(I:C) induces neutrophil extracellular traps via PAD4 to promote inflammation and thrombosis
Biochem Biophys Res Commun. 2021 Jun 4;565:64-71. doi: 10.1016/j.bbrc.2021.05.091. Online ahead of print.ABSTRACTNeutrophil extracellular traps (NETs) are extracellular webs of DNA, histones and granular contents that are released by neutrophils to control infections. However, NETs that is not properly regulated can propagate inflammation and thrombosis. It was recognized that viruses can induce NETs. As a synthetic analog of viral double-stranded (ds) RNA, polyinosinic-polycytidylic acid [poly(I:C)] is known to induce inflammation and thrombosis. However, whether and how poly(I:C) modulates NETs remains unclear. Here, we ...
Source: Biochemical and Biophysical Research communications - June 7, 2021 Category: Biochemistry Authors: Peng Ai Hao Pan Kui Chen Jihang Zheng Zimian Gao Ge Jin Source Type: research

The leukocyte immunoglobulin-like receptor gp49B1, coexpressed with c-Kit, modulates hematopoiesis and B cell leukemia development
Biochem Biophys Res Commun. 2021 Jun 4;565:72-78. doi: 10.1016/j.bbrc.2021.05.090. Online ahead of print.ABSTRACTA better understanding of cell-intrinsic factors involved in regulating stem cells and cancer cells will help advance stem cell applications and cancer cell treatment. Previously, we showed that leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse ortholog, paired immunoglobulin-like receptor B (PIRB), promote blood stem cell and leukemia development. Another unique mouse paralog to PIRB called gp49B1 was also discovered. However, the roles of gp49B1 in hematopoietic stem cells and leukemia developme...
Source: Biochemical and Biophysical Research communications - June 7, 2021 Category: Biochemistry Authors: Huiyun Peng Yizhou Zou Source Type: research

The only conserved microsatellite in coding regions of ebolavirus is the editing site
Biochem Biophys Res Commun. 2021 Jun 4;565:79-84. doi: 10.1016/j.bbrc.2021.05.093. Online ahead of print.ABSTRACTLots of viral genomes were found to contain microsatellites (SSRs) including Ebolavirus, and majority of Ebolavirus microsatellite sites are distributed in protein-coding regions of the genomes. Here, we totally identified 212 reserved microsatellite sites in the protein-coding regions of 213 genomic sequences from five Ebolavirus species. In these reserved microsatellite sites, there is only one significantly conserved microsatellite site among the sample Ebolavirus genomic sequences, and this microsatellite is...
Source: Biochemical and Biophysical Research communications - June 7, 2021 Category: Biochemistry Authors: Douyue Li Ruixue Shi Hongxi Zhang Hanrou Huang Saichao Pan Yuling Liang Shan Peng Zhongyang Tan Source Type: research

Structural insights into two distinct nanobodies recognizing the same epitope of green fluorescent protein
In this study, we determined the crystal structure of the nanobody Nb2 complexed with superfolder GFP (sfGFP) at a resolution of 2.2 Å. Interestingly, although the complementarity-determining regions (CDRs) of Nb2 and LaG16 sequences were only 29.7% identical, they both bound to the same epitope of GFP and existed in the same orientation. Structural analysis indicated that they achieved similar binding characteristics through different mechanisms. We further verified the kinetics and thermodynamics of binding by biolayer interferometry (BLI) and isothermal titration calorimetry (ITC). Nb2 showed a slightly higher bin...
Source: Biochemical and Biophysical Research communications - June 7, 2021 Category: Biochemistry Authors: Peiyu Zhong Ziying Wang Shihao Cheng Yiran Zhang He Jiang Rui Liu Yu Ding Source Type: research

Viral mimetic poly(I:C) induces neutrophil extracellular traps via PAD4 to promote inflammation and thrombosis
Biochem Biophys Res Commun. 2021 Jun 4;565:64-71. doi: 10.1016/j.bbrc.2021.05.091. Online ahead of print.ABSTRACTNeutrophil extracellular traps (NETs) are extracellular webs of DNA, histones and granular contents that are released by neutrophils to control infections. However, NETs that is not properly regulated can propagate inflammation and thrombosis. It was recognized that viruses can induce NETs. As a synthetic analog of viral double-stranded (ds) RNA, polyinosinic-polycytidylic acid [poly(I:C)] is known to induce inflammation and thrombosis. However, whether and how poly(I:C) modulates NETs remains unclear. Here, we ...
Source: Biochemical and Biophysical Research communications - June 7, 2021 Category: Biochemistry Authors: Peng Ai Hao Pan Kui Chen Jihang Zheng Zimian Gao Ge Jin Source Type: research

The leukocyte immunoglobulin-like receptor gp49B1, coexpressed with c-Kit, modulates hematopoiesis and B cell leukemia development
Biochem Biophys Res Commun. 2021 Jun 4;565:72-78. doi: 10.1016/j.bbrc.2021.05.090. Online ahead of print.ABSTRACTA better understanding of cell-intrinsic factors involved in regulating stem cells and cancer cells will help advance stem cell applications and cancer cell treatment. Previously, we showed that leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse ortholog, paired immunoglobulin-like receptor B (PIRB), promote blood stem cell and leukemia development. Another unique mouse paralog to PIRB called gp49B1 was also discovered. However, the roles of gp49B1 in hematopoietic stem cells and leukemia developme...
Source: Biochemical and Biophysical Research communications - June 7, 2021 Category: Biochemistry Authors: Huiyun Peng Yizhou Zou Source Type: research

The only conserved microsatellite in coding regions of ebolavirus is the editing site
Biochem Biophys Res Commun. 2021 Jun 4;565:79-84. doi: 10.1016/j.bbrc.2021.05.093. Online ahead of print.ABSTRACTLots of viral genomes were found to contain microsatellites (SSRs) including Ebolavirus, and majority of Ebolavirus microsatellite sites are distributed in protein-coding regions of the genomes. Here, we totally identified 212 reserved microsatellite sites in the protein-coding regions of 213 genomic sequences from five Ebolavirus species. In these reserved microsatellite sites, there is only one significantly conserved microsatellite site among the sample Ebolavirus genomic sequences, and this microsatellite is...
Source: Biochemical and Biophysical Research communications - June 7, 2021 Category: Biochemistry Authors: Douyue Li Ruixue Shi Hongxi Zhang Hanrou Huang Saichao Pan Yuling Liang Shan Peng Zhongyang Tan Source Type: research

Regulation of autophagy flux by E3 ubiquitin ligase Pirh2 in lung cancer
Biochem Biophys Res Commun. 2021 Jun 2;563:119-125. doi: 10.1016/j.bbrc.2021.05.024. Online ahead of print.ABSTRACTAutophagy is a special catabolic cellular program that is induced in response to deprivation of nutrients and energy starvation. During the execution of this program, cellular components, including aggregates, as well as damaged organelles and some proteins are encapsulated in special vesicles known as autophagosomes and subsequently are degraded after fusion of autophagosomes with lysosomes. Importantly, at late stages of tumorigenesis cancer cells employ autophagy to sustain proliferation in unfavorable cond...
Source: Biochemical and Biophysical Research communications - June 5, 2021 Category: Biochemistry Authors: Olga Fedorova Anastasia Gudovich Alexandra Daks Ekaterina Baidyuk Oleg Shuvalov Alexey Petukhov Sergey Parfenyev Alena Kizenko Nikolai A Barlev Source Type: research

Restoring VTA DA neurons excitability accelerates emergence from sevoflurane general anesthesia of anxiety state
In this study, we report an anxious state results in delayed awakening in anxiety model mice from sevoflurane general anesthesia. More profound inhibition of DA neurons in the VTA contributes to delayed awakening. Optogenetic stimulation of VTA DA neurons can reverse the delay. The results indicate that VTA DA neurons may be involved in the delay in awakening from general anesthesia caused by anxiety.PMID:34090206 | DOI:10.1016/j.bbrc.2021.05.079 (Source: Biochemical and Biophysical Research communications)
Source: Biochemical and Biophysical Research communications - June 5, 2021 Category: Biochemistry Authors: Hui Wang Le Yu Yuan-Jun Qin Ming Chen Xin Wang Huo-Qing Luo Pei-Lin Cong Xiao-Li Wang Hong-Miao Cai Ai-Lian Zhang None Juan-Guo Xiao-Hui Sun Zhao Li Ming Xue Na Sun Qing-Xiu Wang Ji Hu Source Type: research

The X-ray structure of tubulysin analogue TGL in complex with tubulin and three possible routes for the development of next-generation tubulysin analogues
Biochem Biophys Res Commun. 2021 Jun 2;565:29-35. doi: 10.1016/j.bbrc.2021.05.086. Online ahead of print.ABSTRACTMicrotubule-targeting agents (MTAs) are the most commonly used anti-cancer drugs. At least fourteen microtubule inhibitors and ten antibody drug conjugates (ADCs) linking MTAs are approved by FDA for clinical use in cancer therapy. In current research, we determined the crystal structure of tubulysin analogue TGL in complex with tubulin at a high resolution (2.65 Å). In addition, we summarized all of the previously published high-resolution crystal structures of ligands in the vinca site to provide structu...
Source: Biochemical and Biophysical Research communications - June 5, 2021 Category: Biochemistry Authors: Wenting Li Lun Tan Zhixiong Zhang Qiuqi Xia Dongsheng Lei Yuyan Li Ting Zhang Shaoxue Zeng Xiutian Sima Yanyan Wang Source Type: research

Regulatory roles of claudin-1 in cell adhesion and microvilli formation
Biochem Biophys Res Commun. 2021 Jun 2;565:36-42. doi: 10.1016/j.bbrc.2021.05.070. Online ahead of print.ABSTRACTAberrant expression of tight junction proteins has recently been focused on in the cancer research field. We previously showed that claudin-1 is aberrantly expressed from an early stage of uterine cervical adenocarcinoma and contributes to malignant potentials. To elucidate the molecular mechanisms underlying tumor-promoting roles of claudin-1, we established and analyzed claudin-1 knockout cells. Knockout of claudin-1 suppressed conventional tight junctional functions, barrier and fence functions, and expressio...
Source: Biochemical and Biophysical Research communications - June 5, 2021 Category: Biochemistry Authors: Kumi Takasawa Akira Takasawa Taishi Akimoto Kazufumi Magara Tomoyuki Aoyama Hiroshi Kitajima Taro Murakami Yusuke Ono Daisuke Kyuno Hiromu Suzuki Makoto Osanai Source Type: research

Cofilin-1 promotes fibrocyte differentiation and contributes to pulmonary fibrosis
Biochem Biophys Res Commun. 2021 Jun 2;565:43-49. doi: 10.1016/j.bbrc.2021.05.085. Online ahead of print.ABSTRACTFibrocytes originate from the bone marrow monocyte lineage and participate in the pathogenesis of pulmonary fibrosis. Research providing a comprehensive picture of fibrocytes is still limited. Cofilin-1 (CFL-1) is an important protein that regulates cell proliferation, migration and differentiation. Whether CFL-1 can induce monocyte differentiation into fibrocytes and promote the process of pulmonary fibrosis is unknown. Compared with that of healthy controls, the expression of CFL-1 was significantly increased ...
Source: Biochemical and Biophysical Research communications - June 5, 2021 Category: Biochemistry Authors: Wei Guo Ting Guo Qianhui Zhou Yaomei Long Man Luo Qinxue Shen Wang Duan Xiaoli Ouyang Hong Peng Source Type: research

Development of nanobody-based POLArIS orientation probes enabled multi-color/multi-target orientation imaging in living cells
In this study, we have developed new versions of POLArIS with nanobodies, which are compatible with animal immune libraries, and expanded color variations of POLArIS with cyan/green/yellow/red fluorescent proteins, enabling multi-color orientation imaging for multiple targets. Using nanobody-based POLArIS orientation probes, we performed two-color FPM of F-actin and vimentin in living cells. Furthermore, we made nanobody-based POLArIS probes that have different dipole orientations for adjusting the orientation of fluorescence polarization with respect to the target molecules. These nanobody-based POLArIS with options of co...
Source: Biochemical and Biophysical Research communications - June 5, 2021 Category: Biochemistry Authors: Nori Nakai Keisuke Sato Tomomi Tani Masahiko Kawagishi Hiromasa Ka Kenta Saito Sumio Terada Source Type: research

Regulation of autophagy flux by E3 ubiquitin ligase Pirh2 in lung cancer
Biochem Biophys Res Commun. 2021 Jun 2;563:119-125. doi: 10.1016/j.bbrc.2021.05.024. Online ahead of print.ABSTRACTAutophagy is a special catabolic cellular program that is induced in response to deprivation of nutrients and energy starvation. During the execution of this program, cellular components, including aggregates, as well as damaged organelles and some proteins are encapsulated in special vesicles known as autophagosomes and subsequently are degraded after fusion of autophagosomes with lysosomes. Importantly, at late stages of tumorigenesis cancer cells employ autophagy to sustain proliferation in unfavorable cond...
Source: Biochemical and Biophysical Research communications - June 5, 2021 Category: Biochemistry Authors: Olga Fedorova Anastasia Gudovich Alexandra Daks Ekaterina Baidyuk Oleg Shuvalov Alexey Petukhov Sergey Parfenyev Alena Kizenko Nikolai A Barlev Source Type: research

Restoring VTA DA neurons excitability accelerates emergence from sevoflurane general anesthesia of anxiety state
In this study, we report an anxious state results in delayed awakening in anxiety model mice from sevoflurane general anesthesia. More profound inhibition of DA neurons in the VTA contributes to delayed awakening. Optogenetic stimulation of VTA DA neurons can reverse the delay. The results indicate that VTA DA neurons may be involved in the delay in awakening from general anesthesia caused by anxiety.PMID:34090206 | DOI:10.1016/j.bbrc.2021.05.079 (Source: Biochemical and Biophysical Research communications)
Source: Biochemical and Biophysical Research communications - June 5, 2021 Category: Biochemistry Authors: Hui Wang Le Yu Yuan-Jun Qin Ming Chen Xin Wang Huo-Qing Luo Pei-Lin Cong Xiao-Li Wang Hong-Miao Cai Ai-Lian Zhang None Juan-Guo Xiao-Hui Sun Zhao Li Ming Xue Na Sun Qing-Xiu Wang Ji Hu Source Type: research

The X-ray structure of tubulysin analogue TGL in complex with tubulin and three possible routes for the development of next-generation tubulysin analogues
Biochem Biophys Res Commun. 2021 Jun 2;565:29-35. doi: 10.1016/j.bbrc.2021.05.086. Online ahead of print.ABSTRACTMicrotubule-targeting agents (MTAs) are the most commonly used anti-cancer drugs. At least fourteen microtubule inhibitors and ten antibody drug conjugates (ADCs) linking MTAs are approved by FDA for clinical use in cancer therapy. In current research, we determined the crystal structure of tubulysin analogue TGL in complex with tubulin at a high resolution (2.65 Å). In addition, we summarized all of the previously published high-resolution crystal structures of ligands in the vinca site to provide structu...
Source: Biochemical and Biophysical Research communications - June 5, 2021 Category: Biochemistry Authors: Wenting Li Lun Tan Zhixiong Zhang Qiuqi Xia Dongsheng Lei Yuyan Li Ting Zhang Shaoxue Zeng Xiutian Sima Yanyan Wang Source Type: research

Regulatory roles of claudin-1 in cell adhesion and microvilli formation
Biochem Biophys Res Commun. 2021 Jun 2;565:36-42. doi: 10.1016/j.bbrc.2021.05.070. Online ahead of print.ABSTRACTAberrant expression of tight junction proteins has recently been focused on in the cancer research field. We previously showed that claudin-1 is aberrantly expressed from an early stage of uterine cervical adenocarcinoma and contributes to malignant potentials. To elucidate the molecular mechanisms underlying tumor-promoting roles of claudin-1, we established and analyzed claudin-1 knockout cells. Knockout of claudin-1 suppressed conventional tight junctional functions, barrier and fence functions, and expressio...
Source: Biochemical and Biophysical Research communications - June 5, 2021 Category: Biochemistry Authors: Kumi Takasawa Akira Takasawa Taishi Akimoto Kazufumi Magara Tomoyuki Aoyama Hiroshi Kitajima Taro Murakami Yusuke Ono Daisuke Kyuno Hiromu Suzuki Makoto Osanai Source Type: research

Cofilin-1 promotes fibrocyte differentiation and contributes to pulmonary fibrosis
Biochem Biophys Res Commun. 2021 Jun 2;565:43-49. doi: 10.1016/j.bbrc.2021.05.085. Online ahead of print.ABSTRACTFibrocytes originate from the bone marrow monocyte lineage and participate in the pathogenesis of pulmonary fibrosis. Research providing a comprehensive picture of fibrocytes is still limited. Cofilin-1 (CFL-1) is an important protein that regulates cell proliferation, migration and differentiation. Whether CFL-1 can induce monocyte differentiation into fibrocytes and promote the process of pulmonary fibrosis is unknown. Compared with that of healthy controls, the expression of CFL-1 was significantly increased ...
Source: Biochemical and Biophysical Research communications - June 5, 2021 Category: Biochemistry Authors: Wei Guo Ting Guo Qianhui Zhou Yaomei Long Man Luo Qinxue Shen Wang Duan Xiaoli Ouyang Hong Peng Source Type: research

Development of nanobody-based POLArIS orientation probes enabled multi-color/multi-target orientation imaging in living cells
In this study, we have developed new versions of POLArIS with nanobodies, which are compatible with animal immune libraries, and expanded color variations of POLArIS with cyan/green/yellow/red fluorescent proteins, enabling multi-color orientation imaging for multiple targets. Using nanobody-based POLArIS orientation probes, we performed two-color FPM of F-actin and vimentin in living cells. Furthermore, we made nanobody-based POLArIS probes that have different dipole orientations for adjusting the orientation of fluorescence polarization with respect to the target molecules. These nanobody-based POLArIS with options of co...
Source: Biochemical and Biophysical Research communications - June 5, 2021 Category: Biochemistry Authors: Nori Nakai Keisuke Sato Tomomi Tani Masahiko Kawagishi Hiromasa Ka Kenta Saito Sumio Terada Source Type: research

Chemical inhibitor anticancer drugs regulate mechanical properties and cytoskeletal structure of non-invasive and invasive breast cancer cell lines: Study of effects of Letrozole, Exemestane, and Everolimus
In this study, the effects of two Aromatase Inhibitor (Letrozole and Exemestane), and one mTOR Inhibitor (Everolimus) on cell mechanical properties, actin content/distribution, and nuclear areas of two invasive and non-invasive breast cancer cell line after 24 h treatment with concentrations previously reported were investigated. While metabolic activity of cell lines was highly affected by drug treatment, significant alterations in Young's modulus of cell bodies, nuclear areas, and actin content and distribution were reported with higher impact on invasive cells. It was concluded that regulation of mechanical behavior of ...
Source: Biochemical and Biophysical Research communications - June 4, 2021 Category: Biochemistry Authors: Ehsan Mohammadi Mohammad Tabatabaei Mahdi Habibi-Anbouhi Mohammad Tafazzoli-Shadpour Source Type: research

Quantitative circular flow immunoassays with trained object recognition to detect antibodies to SARS-CoV-2 membrane glycoprotein
Biochem Biophys Res Commun. 2021 May 29;565:8-13. doi: 10.1016/j.bbrc.2021.05.073. Online ahead of print.ABSTRACTAmidst infectious disease outbreaks, a practical tool that can quantitatively monitor individuals' antibodies to pathogens is vital for disease control. The currently used serological lateral flow immunoassays (LFIAs) can only detect the presence of antibodies for a single antigen. Here, we fabricated a multiplexed circular flow immunoassay (CFIA) test strip with YOLO v4-based object recognition that can quickly quantify and differentiate antibodies that bind membrane glycoprotein of severe acute respiratory syn...
Source: Biochemical and Biophysical Research communications - June 4, 2021 Category: Biochemistry Authors: Ryan Yuki Huang Deron Raymond Herr Source Type: research

The Spf1p P5A-ATPase "arm-like" domain is not essential for ATP hydrolysis but its deletion impairs autophosphorylation
Biochem Biophys Res Commun. 2021 Jun 1;563:113-118. doi: 10.1016/j.bbrc.2021.05.054. Online ahead of print.ABSTRACTThe yeast Spf1p P5A-ATPase actively translocates membrane spanning peptides of mislocalized proteins from the endoplasmic reticulum. Loss of Spf1p function causes a pleiotropic ER stress-phenotype associated with alterations of homeostasis of metal ions, lipids, protein folding, glycosylation, and membrane insertion. A unique characteristic of P5A-ATPases is the presence of an extended insertion which was called the "arm-like" domain connecting the phosphorylation domain (P) with transmembrane segmen...
Source: Biochemical and Biophysical Research communications - June 4, 2021 Category: Biochemistry Authors: Paula Grenon Gerardo R Corradi Guido D Petrovich Luciana R Mazzitelli Hugo P Adamo Source Type: research

Chemical inhibitor anticancer drugs regulate mechanical properties and cytoskeletal structure of non-invasive and invasive breast cancer cell lines: Study of effects of Letrozole, Exemestane, and Everolimus
In this study, the effects of two Aromatase Inhibitor (Letrozole and Exemestane), and one mTOR Inhibitor (Everolimus) on cell mechanical properties, actin content/distribution, and nuclear areas of two invasive and non-invasive breast cancer cell line after 24 h treatment with concentrations previously reported were investigated. While metabolic activity of cell lines was highly affected by drug treatment, significant alterations in Young's modulus of cell bodies, nuclear areas, and actin content and distribution were reported with higher impact on invasive cells. It was concluded that regulation of mechanical behavior of ...
Source: Biochemical and Biophysical Research communications - June 4, 2021 Category: Biochemistry Authors: Ehsan Mohammadi Mohammad Tabatabaei Mahdi Habibi-Anbouhi Mohammad Tafazzoli-Shadpour Source Type: research

Quantitative circular flow immunoassays with trained object recognition to detect antibodies to SARS-CoV-2 membrane glycoprotein
Biochem Biophys Res Commun. 2021 May 29;565:8-13. doi: 10.1016/j.bbrc.2021.05.073. Online ahead of print.ABSTRACTAmidst infectious disease outbreaks, a practical tool that can quantitatively monitor individuals' antibodies to pathogens is vital for disease control. The currently used serological lateral flow immunoassays (LFIAs) can only detect the presence of antibodies for a single antigen. Here, we fabricated a multiplexed circular flow immunoassay (CFIA) test strip with YOLO v4-based object recognition that can quickly quantify and differentiate antibodies that bind membrane glycoprotein of severe acute respiratory syn...
Source: Biochemical and Biophysical Research communications - June 4, 2021 Category: Biochemistry Authors: Ryan Yuki Huang Deron Raymond Herr Source Type: research

The Spf1p P5A-ATPase "arm-like" domain is not essential for ATP hydrolysis but its deletion impairs autophosphorylation
Biochem Biophys Res Commun. 2021 Jun 1;563:113-118. doi: 10.1016/j.bbrc.2021.05.054. Online ahead of print.ABSTRACTThe yeast Spf1p P5A-ATPase actively translocates membrane spanning peptides of mislocalized proteins from the endoplasmic reticulum. Loss of Spf1p function causes a pleiotropic ER stress-phenotype associated with alterations of homeostasis of metal ions, lipids, protein folding, glycosylation, and membrane insertion. A unique characteristic of P5A-ATPases is the presence of an extended insertion which was called the "arm-like" domain connecting the phosphorylation domain (P) with transmembrane segmen...
Source: Biochemical and Biophysical Research communications - June 4, 2021 Category: Biochemistry Authors: Paula Grenon Gerardo R Corradi Guido D Petrovich Luciana R Mazzitelli Hugo P Adamo Source Type: research

Characterization of a putative maltodextrin-binding protein of Streptococcus pyogenes, SPs0871 and the development of a VHH inhibitor
Biochem Biophys Res Commun. 2021 May 30;565:1-7. doi: 10.1016/j.bbrc.2021.05.056. Online ahead of print.ABSTRACTStreptococcus pyogenes causes a wide range of human infections. Currently, antibiotics are the main treatment for S. pyogenes infection, but serious anti-microbial resistance requires alternative treatment options. To develop a novel strategy for treatment, we physicochemically characterized SPs0871, a putative maltose/maltodextrin-binding protein that is thought to have important roles in the pathogenesis of invasive streptococci. We obtained a variable domain of heavy chain of heavy-chain antibody, the smallest...
Source: Biochemical and Biophysical Research communications - June 2, 2021 Category: Biochemistry Authors: Tsukushi Yamawaki Makoto Nakakido Kan Ujiie Chihiro Aikawa Ichiro Nakagawa Kouhei Tsumoto Source Type: research

PSMD9 ribosomal protein network maintains nucleolar architecture and WT p53 levels
Biochem Biophys Res Commun. 2021 May 30;563:105-112. doi: 10.1016/j.bbrc.2021.05.004. Online ahead of print.ABSTRACTCapitalizing on an unexpected observation that multiple free ribosomal proteins co-purify/pull-down with PSMD9, we report here for the first time that PSMD9 is necessary to maintain the morphology and integrity of the nucleolus. As seen by NPM1 immunofluorescence and electron microscopy, the nucleolar structure is clearly disrupted in PSMD9 null MCF7 breast cancer cells. The resultant stress is pronounced leading to the accumulation of WT p53 and slow growth. A dual insult with Actinomycin D exasperates the n...
Source: Biochemical and Biophysical Research communications - June 2, 2021 Category: Biochemistry Authors: Sheikh Burhan Ud Din Farooqee Joel Christie Prasanna Venkatraman Source Type: research

Characterization of a putative maltodextrin-binding protein of Streptococcus pyogenes, SPs0871 and the development of a VHH inhibitor
Biochem Biophys Res Commun. 2021 May 30;565:1-7. doi: 10.1016/j.bbrc.2021.05.056. Online ahead of print.ABSTRACTStreptococcus pyogenes causes a wide range of human infections. Currently, antibiotics are the main treatment for S. pyogenes infection, but serious anti-microbial resistance requires alternative treatment options. To develop a novel strategy for treatment, we physicochemically characterized SPs0871, a putative maltose/maltodextrin-binding protein that is thought to have important roles in the pathogenesis of invasive streptococci. We obtained a variable domain of heavy chain of heavy-chain antibody, the smallest...
Source: Biochemical and Biophysical Research communications - June 2, 2021 Category: Biochemistry Authors: Tsukushi Yamawaki Makoto Nakakido Kan Ujiie Chihiro Aikawa Ichiro Nakagawa Kouhei Tsumoto Source Type: research

PSMD9 ribosomal protein network maintains nucleolar architecture and WT p53 levels
Biochem Biophys Res Commun. 2021 May 30;563:105-112. doi: 10.1016/j.bbrc.2021.05.004. Online ahead of print.ABSTRACTCapitalizing on an unexpected observation that multiple free ribosomal proteins co-purify/pull-down with PSMD9, we report here for the first time that PSMD9 is necessary to maintain the morphology and integrity of the nucleolus. As seen by NPM1 immunofluorescence and electron microscopy, the nucleolar structure is clearly disrupted in PSMD9 null MCF7 breast cancer cells. The resultant stress is pronounced leading to the accumulation of WT p53 and slow growth. A dual insult with Actinomycin D exasperates the n...
Source: Biochemical and Biophysical Research communications - June 2, 2021 Category: Biochemistry Authors: Sheikh Burhan Ud Din Farooqee Joel Christie Prasanna Venkatraman Source Type: research

Acylated peptide enrichment utilizing lysine deacylases for lysine acylomics
In this study, we developed a novel enrichment method for acylated peptides without the use of antibodies, in which endogenously acylated peptides are deacylated by recombinant lysine deacylases based on the enzyme-substrate relationship and enriched by N-hydroxysuccinimidyl chemistry for identification of the acylated sites by nanoscale liquid chromatography-tandem mass spectrometric analysis. To demonstrate the validity of this acylomics platform, we used it to identify acylated sites on chemically acylated model protein samples. We also applied it to the nuclei of HeLa cells to identify endogenous acylated sites.PMID:34...
Source: Biochemical and Biophysical Research communications - June 1, 2021 Category: Biochemistry Authors: Kazuya Tsumagari Yasushi Ishihama Source Type: research

Comprehensive expression pattern of kin of irregular chiasm-like 3 in the adult mouse brain
Biochem Biophys Res Commun. 2021 May 29;563:66-72. doi: 10.1016/j.bbrc.2021.05.063. Online ahead of print.ABSTRACTKin of irregular chiasm-like 3 (Kirrel3), a member of the immunoglobulin superfamily, is expressed in the central nervous system during development and in adulthood. It has been reported that Kirrel3 is involved in the axonal fasciculation in the olfactory bulb, the neuronal migration in the pontine nucleus, and the synapse formation in the hippocampal neurons in mice. Although KIRREL3 mutations have been implicated in autism spectrum disorder and intellectual disability in humans, the comprehensive expression ...
Source: Biochemical and Biophysical Research communications - June 1, 2021 Category: Biochemistry Authors: Tomoko Hisaoka Tadasuke Komori Kohta Fujimoto Toshio Kitamura Yoshihiro Morikawa Source Type: research

Monopolar flocking of microtubules in collective motion
Biochem Biophys Res Commun. 2021 May 29;563:73-78. doi: 10.1016/j.bbrc.2021.05.037. Online ahead of print.ABSTRACTFlocking is a fascinating coordinated behavior of living organisms or self-propelled particles (SPPs). Particularly, monopolar flocking has been attractive due to its potential applications in various fields. However, the underlying mechanism behind flocking and emergence of monopolar motion in flocking of SPPs has remained obscured. Here, we demonstrate monopolar flocking of kinesin-driven microtubules, a self-propelled biomolecular motor system. Microtubules with an intrinsic structural chirality preferential...
Source: Biochemical and Biophysical Research communications - June 1, 2021 Category: Biochemistry Authors: Farhana Afroze Daisuke Inoue Tamanna Ishrat Farhana Tetsuya Hiraiwa Ryo Akiyama Arif Md Rashedul Kabir Kazuki Sada Akira Kakugo Source Type: research

Sequence determinants of human junctophilin-2 protein nuclear localization and phase separation
Biochem Biophys Res Commun. 2021 May 29;563:79-84. doi: 10.1016/j.bbrc.2021.05.078. Online ahead of print.ABSTRACTJunctophilin-2 (JPH2) was conventionally considered as a structural membrane binding protein. Recently, it was shown that proteolytically truncated mouse JPH2 variants are imported into nucleus to exert alternative functions. However, the intranuclear behaviors of human JPH2 (hJPH2) and underlying molecular determinants have not been explored. Here, we demonstrate that full-length hJPH2 is imported into nucleus in human cells by two nuclear localization signals (NLSs), including a newly discovered one at the C-...
Source: Biochemical and Biophysical Research communications - June 1, 2021 Category: Biochemistry Authors: Ang Guo Wenjuan Fang Savannah Gibson Source Type: research

The leucine-rich repeat receptor-like kinase OsERL plays a critical role in anther lobe formation in rice
In this study, sixty-seven TILLING and four gene-edited mutants were identified for one of the three OsERs, OsERL, and used for functional analyses. Results showed that mutations in OsERL led to striking defects in anther development. Compete male sterility and reduced numbers of anther lobes, more severe than knockout mutants, were observed in mutants with amino acid substitutions in the kinase domain. Among alleles with amino acid changes in LRRs, only one mutation in the 16th LRR showed evident phenotype, suggesting a role of the LRR in ligand sensing. OsERL is expressed in shoot apcies, internodes and anthers, and with...
Source: Biochemical and Biophysical Research communications - June 1, 2021 Category: Biochemistry Authors: Ting Liu Guo-Qiang Jiang Xue-Feng Yao Chun-Ming Liu Source Type: research

Similarities and differences in the conformational stability and reversibility of ORF8, an accessory protein of SARS-CoV-2, and its L84S variant
In this study, the physicochemical properties of the wild-type ORF8 and its L84S variant were analyzed and compared. Using the tobacco BY-2 cell production system, which has been successfully used to produce the wild-type ORF8 protein with a single conformation, was used to successfully produce the ORF8 L84S variant protein at the same level as wild-type ORF8. The produced proteins were purified, and their temperature and pH dependencies were examined using nuclear magnetic resonance spectra. Our data suggested that the wild-type and L84S variant ORF8 structures are highly stable over a wide temperature range. Both protein...
Source: Biochemical and Biophysical Research communications - June 1, 2021 Category: Biochemistry Authors: Shinya Ohki Tomohiro Imamura Yasuki Higashimura Kenji Matsumoto Masashi Mori Source Type: research

ZNF746/PARIS promotes the occurrence of hepatocellular carcinoma
Biochem Biophys Res Commun. 2021 May 29;563:98-104. doi: 10.1016/j.bbrc.2021.05.051. Online ahead of print.ABSTRACTHepatocellular carcinoma (HCC) is the most common primary liver cancer to cause liver cancer related deaths worldwide. Zinc finger protein 746 (ZNF746), initially identified as a Parkin-interacting substrate (PARIS), acts as a transcriptional repressor of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in Parkinson's disease. As recent studies reported that PARIS is associated with cancer onset, we investigated whether PARIS is associated with HCC. We found an increase in...
Source: Biochemical and Biophysical Research communications - June 1, 2021 Category: Biochemistry Authors: Hanna Kim Ji-Yeong Lee Soo Jeong Park Eunsang Kwag Okjae Koo Joo-Ho Shin Source Type: research

Acylated peptide enrichment utilizing lysine deacylases for lysine acylomics
In this study, we developed a novel enrichment method for acylated peptides without the use of antibodies, in which endogenously acylated peptides are deacylated by recombinant lysine deacylases based on the enzyme-substrate relationship and enriched by N-hydroxysuccinimidyl chemistry for identification of the acylated sites by nanoscale liquid chromatography-tandem mass spectrometric analysis. To demonstrate the validity of this acylomics platform, we used it to identify acylated sites on chemically acylated model protein samples. We also applied it to the nuclei of HeLa cells to identify endogenous acylated sites.PMID:34...
Source: Biochemical and Biophysical Research communications - June 1, 2021 Category: Biochemistry Authors: Kazuya Tsumagari Yasushi Ishihama Source Type: research

Comprehensive expression pattern of kin of irregular chiasm-like 3 in the adult mouse brain
Biochem Biophys Res Commun. 2021 May 29;563:66-72. doi: 10.1016/j.bbrc.2021.05.063. Online ahead of print.ABSTRACTKin of irregular chiasm-like 3 (Kirrel3), a member of the immunoglobulin superfamily, is expressed in the central nervous system during development and in adulthood. It has been reported that Kirrel3 is involved in the axonal fasciculation in the olfactory bulb, the neuronal migration in the pontine nucleus, and the synapse formation in the hippocampal neurons in mice. Although KIRREL3 mutations have been implicated in autism spectrum disorder and intellectual disability in humans, the comprehensive expression ...
Source: Biochemical and Biophysical Research communications - June 1, 2021 Category: Biochemistry Authors: Tomoko Hisaoka Tadasuke Komori Kohta Fujimoto Toshio Kitamura Yoshihiro Morikawa Source Type: research

Monopolar flocking of microtubules in collective motion
Biochem Biophys Res Commun. 2021 May 29;563:73-78. doi: 10.1016/j.bbrc.2021.05.037. Online ahead of print.ABSTRACTFlocking is a fascinating coordinated behavior of living organisms or self-propelled particles (SPPs). Particularly, monopolar flocking has been attractive due to its potential applications in various fields. However, the underlying mechanism behind flocking and emergence of monopolar motion in flocking of SPPs has remained obscured. Here, we demonstrate monopolar flocking of kinesin-driven microtubules, a self-propelled biomolecular motor system. Microtubules with an intrinsic structural chirality preferential...
Source: Biochemical and Biophysical Research communications - June 1, 2021 Category: Biochemistry Authors: Farhana Afroze Daisuke Inoue Tamanna Ishrat Farhana Tetsuya Hiraiwa Ryo Akiyama Arif Md Rashedul Kabir Kazuki Sada Akira Kakugo Source Type: research

Sequence determinants of human junctophilin-2 protein nuclear localization and phase separation
Biochem Biophys Res Commun. 2021 May 29;563:79-84. doi: 10.1016/j.bbrc.2021.05.078. Online ahead of print.ABSTRACTJunctophilin-2 (JPH2) was conventionally considered as a structural membrane binding protein. Recently, it was shown that proteolytically truncated mouse JPH2 variants are imported into nucleus to exert alternative functions. However, the intranuclear behaviors of human JPH2 (hJPH2) and underlying molecular determinants have not been explored. Here, we demonstrate that full-length hJPH2 is imported into nucleus in human cells by two nuclear localization signals (NLSs), including a newly discovered one at the C-...
Source: Biochemical and Biophysical Research communications - June 1, 2021 Category: Biochemistry Authors: Ang Guo Wenjuan Fang Savannah Gibson Source Type: research