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Source: Journal of Biological Chemistry

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Total 602 results found since Jan 2013.

Tyrosine phosphorylation of the scaffold protein IQGAP1 in the MET pathway alters function Signal Transduction
IQGAP1 is a key scaffold protein that regulates numerous cellular processes and signaling pathways. Analogous to many other cellular proteins, IQGAP1 undergoes post-translational modifications, including phosphorylation. Nevertheless, very little is known about the specific sites of phosphorylation or the effects on IQGAP1 function. Here, using several approaches, including MS, site-directed mutagenesis, siRNA-mediated gene silencing, and chemical inhibitors, we identified the specific tyrosine residues that are phosphorylated on IQGAP1 and evaluated the effect on function. Tyr-172, Tyr-654, Tyr-855, and Tyr-1510 were phos...
Source: Journal of Biological Chemistry - December 25, 2020 Category: Chemistry Authors: Andrew C. Hedman, Dean E. McNulty, Zhigang Li, Laetitia Gorisse, Roland S. Annan, David B. Sacks Tags: Signal Transduction Source Type: research

Hepatocyte nuclear factor 1{beta} suppresses canonical Wnt signaling through transcriptional repression of lymphoid enhancer-binding factor 1 Molecular Bases of Disease
Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is required for normal kidney development and renal epithelial differentiation. Mutations of HNF-1β produce congenital kidney abnormalities and inherited renal tubulopathies. Here, we show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer–binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. Expression...
Source: Journal of Biological Chemistry - December 18, 2020 Category: Chemistry Authors: Siu Chiu Chan, Sachin S. Hajarnis, Sophia M. Vrba, Vishal Patel, Peter Igarashi Tags: Gene Regulation Source Type: research

Dysregulation of hsa-miR-34a and hsa-miR-449a leads to overexpression of PACS-1 and loss of DNA damage response (DDR) in cervical cancer Cell Biology
We have observed overexpression of PACS-1, a cytosolic sorting protein in primary cervical tumors. Absence of exonic mutations and overexpression at the RNA level suggested a transcriptional and/or posttranscriptional regulation. University of California Santa Cruz genome browser analysis of PACS-1 micro RNAs (miR), revealed two 8-base target sequences at the 3′ terminus for hsa-miR-34a and hsa-miR-449a. Quantitative RT-PCR and Northern blotting studies showed reduced or loss of expression of the two microRNAs in cervical cancer cell lines and primary tumors, indicating dysregulation of these two microRNAs in cervical ca...
Source: Journal of Biological Chemistry - December 11, 2020 Category: Chemistry Authors: Mysore S. Veena, Santanu Raychaudhuri, Saroj K. Basak, Natarajan Venkatesan, Parameet Kumar, Roopa Biswas, Rita Chakrabarti, Jing Lu, Trent Su, Marcus Gallagher-Jones, Marco Morselli, Haiqing Fu, Matteo Pellegrini, Theodore Goldstein, Mirit I. Aladjem, Ma Tags: Molecular Bases of Disease Source Type: research

Angiotensin AT1 receptor antagonism by losartan stimulates adipocyte browning via induction of apelin Cell Biology
Adipocyte browning appears to be a potential therapeutic strategy to combat obesity and related metabolic disorders. Recent studies have shown that apelin, an adipokine, stimulates adipocyte browning and has negative cross-talk with angiotensin II receptor type 1 (AT1 receptor) signaling. Here, we report that losartan, a selective AT1 receptor antagonist, induces browning, as evidenced by an increase in browning marker expression, mitochondrial biogenesis, and oxygen consumption in murine adipocytes. In parallel, losartan up-regulated apelin expression, concomitant with increased phosphorylation of protein kinase B and AMP...
Source: Journal of Biological Chemistry - October 30, 2020 Category: Chemistry Authors: Dong Young Kim, Mi Jin Choi, Tae Kyung Ko, Na Hyun Lee, Ok-Hee Kim, Hyae Gyeong Cheon Tags: Cell Biology Source Type: research

Regulation of the thrombin/protease-activated receptor 1 axis by chemokine (CXC motif) receptor 4 Cell Biology
The chemokine receptor CXCR4, a G protein–coupled receptor (GPCR) capable of heteromerizing with other GPCRs, is involved in many processes, including immune responses, hematopoiesis, and organogenesis. Evidence suggests that CXCR4 activation reduces thrombin/protease-activated receptor 1 (PAR1)-induced impairment of endothelial barrier function. However, the mechanisms underlying cross-talk between CXCR4 and PAR1 are not well-understood. Using intermolecular bioluminescence resonance energy transfer and proximity ligation assays, we found that CXCR4 heteromerizes with PAR1 in the HEK293T expression system and in human p...
Source: Journal of Biological Chemistry - October 30, 2020 Category: Chemistry Authors: Xianlong Gao, You-Hong Cheng, Garrett A. Enten, Anthony J. DeSantis, Vadim Gaponenko, Matthias Majetschak Tags: Signal Transduction Source Type: research

Combined p53- and PTEN-deficiency activates expression of mesenchyme homeobox 1 (MEOX1) required for growth of triple-negative breast cancer Molecular Bases of Disease
In this study, we discovered that combined p53- and PTEN-deficiency in TNBC activates expression of the transcription factor mesenchyme homeobox 1 (MEOX1). We found that MEOX1 is expressed only in TNBC cells with frequent deficiencies in p53 and PTEN, and that its expression is undetectable in luminal A, luminal B, and HER2+ subtypes, as well as in normal breast cells with wild-type (WT) p53 and PTEN. Notably, siRNA knockdown of both p53 and PTEN activated MEOX1 expression in breast cancer cells, whereas individual knockdowns of either p53 or PTEN had only minimal effects on MEOX1 expression. MEOX1 knockdown abolished cell...
Source: Journal of Biological Chemistry - August 20, 2020 Category: Chemistry Authors: Mari Gasparyan, Miao-Chia Lo, Hui Jiang, Chang-Ching Lin, Duxin Sun Tags: Molecular Bases of Disease Source Type: research

The WD40-repeat protein WDR-48 promotes the stability of the deubiquitinating enzyme USP-46 by inhibiting its ubiquitination and degradation Cell Biology
Ubiquitination is a reversible post-translational modification that has emerged as a critical regulator of synapse development and function. However, the mechanisms that regulate the deubiquitinating enzymes (DUBs) responsible for the removal of ubiquitin from target proteins are poorly understood. We have previously shown that the DUB ubiquitin-specific protease 46 (USP-46) removes ubiquitin from the glutamate receptor GLR-1 and regulates its trafficking and degradation in Caenorhabditis elegans. We found that the WD40-repeat proteins WDR-20 and WDR-48 bind and stimulate the catalytic activity of USP-46. Here, we identifi...
Source: Journal of Biological Chemistry - August 13, 2020 Category: Chemistry Authors: Molly Hodul, Rakesh Ganji, Caroline L. Dahlberg, Malavika Raman, Peter Juo Tags: Protein Synthesis and Degradation Source Type: research

The NADPH oxidase NOX4 promotes the directed migration of endothelial cells by stabilizing vascular endothelial growth factor receptor 2 protein Protein Synthesis and Degradation
Directed migration of endothelial cells (ECs) is an important process during both physiological and pathological angiogenesis. The binding of vascular endothelial growth factor (VEGF) to VEGF receptor-2 (VEGFR-2) on the EC surface is necessary for directed migration of these cells. Here, we used TAXIScan, an optically accessible real-time horizontal cell dynamics assay approach, and demonstrate that reactive oxygen species (ROS)-producing NADPH oxidase 4 (NOX4), which is abundantly expressed in ECs, mediates VEGF/VEGFR-2-dependent directed migration. We noted that a continuous supply of endoplasmic reticulum (ER)-retained ...
Source: Journal of Biological Chemistry - August 13, 2020 Category: Chemistry Authors: Kei Miyano, Shuichiro Okamoto, Akira Yamauchi, Chikage Kawai, Mizuho Kajikawa, Takuya Kiyohara, Minoru Tamura, Masahiko Taura, Futoshi Kuribayashi Tags: Protein Synthesis and Degradation Source Type: research

Correction: A novel CXCR3-B chemokine receptor-induced growth-inhibitory signal in cancer cells is mediated through the regulation of Bach-1 protein and Nrf2 protein nuclear translocation. Additions and Corrections
VOLUME 289 (2014) PAGES 3126–3137There was an error in Fig 6C. The dot plot in panel 1 (Control siRNA + Vector) was mistakenly duplicated with the dot plot in panel 4 (Bach-1 siRNA + CXCR3-B). However, the numbers of the % apoptotic cells were correct. This error happened inadvertently during the preparation of the figure panels. This error has now been corrected and does not affect the results or conclusions of the work reported in this study. The authors apologize for this error.jbc;295/30/10509/F6F1F6Figure 6.
Source: Journal of Biological Chemistry - July 23, 2020 Category: Chemistry Authors: Murugabaskar Balan, Soumitro Pal Tags: Additions and Corrections Source Type: research

Chronic treatment with the complex I inhibitor MPP+ depletes endogenous PTEN-induced kinase 1 (PINK1) via up-regulation of Bcl-2-associated athanogene 6 (BAG6) Neurobiology
Mitochondrial dysfunction is implicated in sporadic and familial Parkinson's disease (PD). However, the mechanisms that impair homeostatic responses to mitochondrial dysfunction remain unclear. Previously, we found that chronic, low-dose administration of the mitochondrial complex I inhibitor 1-methyl-4-phenylpyridinium (MPP+) dysregulates mitochondrial fission–fusion, mitophagy, and mitochondrial biogenesis. Given that PTEN-induced kinase 1 (PINK1) regulates mitochondrial function, dynamics, and turnover, we hypothesized that alterations in endogenous PINK1 levels contribute to depletion of mitochondria during chronic c...
Source: Journal of Biological Chemistry - June 4, 2020 Category: Chemistry Authors: Manish Verma, Jianhui Zhu, Kent Z. Q. Wang, Charleen T. Chu Tags: Molecular Bases of Disease Source Type: research

Host ESCRT factors are recruited during chikungunya virus infection and are required for the intracellular viral replication cycle Cell Biology
Chikungunya fever is a re-emerging zoonotic disease caused by chikungunya virus (CHIKV), a member of the Alphavirus genus in the Togaviridae family. Only a few studies have reported on the host factors required for intracellular CHIKV trafficking. Here, we conducted an imaging-based siRNA screen to identify human host factors for intracellular trafficking that are involved in CHIKV infection, examined their interactions with CHIKV proteins, and investigated the contributions of these proteins to CHIKV infection. The results of the siRNA screen revealed that host endosomal sorting complexes required for transport (ESCRT) pr...
Source: Journal of Biological Chemistry - June 4, 2020 Category: Chemistry Authors: Shiho Torii, Yasuko Orba, Michihito Sasaki, Koshiro Tabata, Yuji Wada, Michael Carr, Jody Hobson-Peters, Roy A. Hall, Ayato Takada, Takasuke Fukuhara, Yoshiharu Matsuura, William W. Hall, Hirofumi Sawa Tags: Microbiology Source Type: research

The mRNA encoding the JUND tumor suppressor detains nuclear RNA-binding proteins to assemble polysomes that are unaffected by mTOR Protein Synthesis and Degradation
We present evidence from reciprocal immunoprecipitation experiments indicating that NCBP1 and RHA both are components of messenger ribonucleoproteins in several cell types. Moreover, tandem affinity and RT–quantitative PCR results revealed that JUND mRNA is a component of a previously unknown ribonucleoprotein complex. Results from the tandem IP indicated that another component of the JUND-containing ribonucleoprotein complex is NCBP3, a recently identified ortholog of NCBP2/CBP20. We also found that NCBP1, NCBP3, and RHA, but not NCBP2, are components of JUND-containing polysomes. Mutational analysis uncovered two dsRNA...
Source: Journal of Biological Chemistry - May 28, 2020 Category: Chemistry Authors: Gatikrushna Singh, Sarah E. Fritz, Bradley Seufzer, Kathleen Boris-Lawrie Tags: Cell Biology Source Type: research

Mycosporine-like amino acids stimulate hyaluronan secretion by up-regulating hyaluronan synthase 2 via activation of the p38/MSK1/CREB/c-Fos/AP-1 axis Signal Transduction
Hyaluronan (HA) is an extracellular matrix glycosaminoglycan that critically supports the physicochemical and mechanical properties of the skin. Here, we demonstrate that mycosporine-like amino acids (MAAs), which typically function as UV-absorbing compounds, can stimulate HA secretion from normal human fibroblasts. MAA-stimulated HA secretion was associated with significantly increased and decreased levels of mRNAs encoding HA synthase 2 (HAS2) and the HA-binding protein involved in HA depolymerization (designated HYBID), respectively. Using immunoblotting, we found that MAAs at 10 and at 25 μg/ml stimulate the phosphory...
Source: Journal of Biological Chemistry - May 21, 2020 Category: Chemistry Authors: Shuko Terazawa, Masahiko Nakano, Akio Yamamoto, Genji Imokawa Tags: Signal Transduction Source Type: research

The gene for the lysosomal protein LAMP3 is a direct target of the transcription factor ATF4 Gene Regulation
Autophagy and lysosomal activities play a key role in the cell by initiating and carrying out the degradation of misfolded proteins. Transcription factor EB (TFEB) functions as a master controller of lysosomal biogenesis and function during lysosomal stress, controlling most but, importantly, not all lysosomal genes. Here, we sought to better understand the regulation of lysosomal genes whose expression does not appear to be controlled by TFEB. Sixteen of these genes were screened for transactivation in response to diverse cellular insults. mRNA levels for lysosomal-associated membrane protein 3 (LAMP3), a gene that is hig...
Source: Journal of Biological Chemistry - May 21, 2020 Category: Chemistry Authors: Thomas D. Burton, Anthony O. Fedele, Jianling Xie, Lauren Y. Sandeman, Christopher G. Proud Tags: Gene Regulation Source Type: research

Arachidonate 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid contribute to stromal aging-induced progression of pancreatic cancer Molecular Bases of Disease
In this study, we investigated whether the chronological aging of normal human fibroblasts (NHFs), a previously underappreciated area in pancreatic cancer research, influences the progression and therapeutic outcomes of PDAC. Results from experiments with murine xenografts and 2D and 3D co-cultures of NHFs and PDAC cells revealed that older NHFs stimulate proliferation of and confer resistance to radiation therapy of PDAC. MS-based metabolite analysis indicated that older NHFs have significantly increased arachidonic acid 12-lipoxygenase (ALOX12) expression and elevated levels of its mitogenic metabolite, 12-(S)-hydroxy-5,...
Source: Journal of Biological Chemistry - May 14, 2020 Category: Chemistry Authors: Ehab H. Sarsour, Jyung Mean Son, Amanda L. Kalen, Wusheng Xiao, Juan Du, Matthew S. Alexander, Brianne R. O'Leary, Joseph J. Cullen, Prabhat C. Goswami Tags: Cell Biology Source Type: research