Cellular and Molecular Life Sciences : CMLS This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Probing of the reactive center loop region of alpha-1-antitrypsin by mutagenesis predicts new type-2 dysfunctional variants
Cell Mol Life Sci. 2023 Dec 13;81(1):6. doi: 10.1007/s00018-023-05059-1.ABSTRACTLung disease in alpha-1-antitrypsin deficiency (AATD) mainly results from insufficient control of the serine proteases neutrophil elastase (NE) and proteinase-3 due to reduced plasma levels of alpha-1-antitrypsin (AAT) variants. Mutations in the specificity-determining reactive center loop (RCL) of AAT would be predicted to minimally affect protein folding and secretion by hepatocytes but can impair anti-protease activity or alter the target protease. These properly secreted but dysfunctional 'type-2' variants would not be identified by common ...
Source: Cellular and Molecular Life Sciences : CMLS - December 12, 2023 Category: Cytology Authors: Andrea Denardo Emna Ben Khlifa Mattia Bignotti Roberta Giuliani Emanuela D'Acunto Elena Miranda James A Irving Annamaria Fra Source Type: research

SHP2 clinical phenotype, cancer, or RASopathies, can be predicted by mutant conformational propensities
Cell Mol Life Sci. 2023 Dec 12;81(1):5. doi: 10.1007/s00018-023-05052-8.ABSTRACTSHP2 phosphatase promotes full activation of the RTK-dependent Ras/MAPK pathway. Its mutations can drive cancer and RASopathies, a group of neurodevelopmental disorders (NDDs). Here we ask how same residue mutations in SHP2 can lead to both cancer and NDD phenotypes, and whether we can predict what the outcome will be. We collected and analyzed mutation data from the literature and cancer databases and performed molecular dynamics simulations of SHP2 mutants. We show that both cancer and Noonan syndrome (NS, a RASopathy) mutations favor catalys...
Source: Cellular and Molecular Life Sciences : CMLS - December 12, 2023 Category: Cytology Authors: Yonglan Liu Wengang Zhang Hyunbum Jang Ruth Nussinov Source Type: research

Myeloid SENP3 deficiency protects mice from diet and age-induced obesity via regulation of YAP1 SUMOylation
Cell Mol Life Sci. 2023 Dec 9;81(1):4. doi: 10.1007/s00018-023-05050-w.ABSTRACTObesity is characterized by chronic low-grade inflammation, which is driven by macrophage infiltration in adipose tissue and leads to elevated cytokines such as interleukin-1β (IL-1β) in the circulation and tissues. Previous studies demonstrate that SENP3, a redox-sensitive SUMO2/3-specific protease, is strongly implicated in the development and progression of cancer and cardiovascular diseases. However, the role of SENP3 in obesity-associated inflammation remains largely unknown. To better understand the effects of SENP3 on adipose tissue mac...
Source: Cellular and Molecular Life Sciences : CMLS - December 9, 2023 Category: Cytology Authors: Yangjing Jiang Min Liang Long Chen Jian Wang Yijie Huang Huanhuan Huo Danrui Xiao Yunwen Hu Zi Wang Qingqi Ji Yanjie Li Zhaohua Cai Ben He Source Type: research

Mfsd7b facilitates choline transport and missense mutations affect choline transport function
Cell Mol Life Sci. 2023 Dec 6;81(1):3. doi: 10.1007/s00018-023-05048-4.ABSTRACTMFSD7b belongs to the Major Facilitator Superfamily of transporters that transport small molecules. Two isoforms of MFSD7b have been identified and they are reported to be heme exporters that play a crucial role in maintaining the cytosolic and mitochondrial heme levels, respectively. Mutations of MFSD7b (also known as FLVCR1) have been linked to retinitis pigmentosa, posterior column ataxia, and hereditary sensory and autonomic neuropathy. Although MFSD7b functions have been linked to heme detoxification by exporting excess heme from erythroid ...
Source: Cellular and Molecular Life Sciences : CMLS - December 6, 2023 Category: Cytology Authors: Hoa Thi Thuy Ha Viresh Krishnan Sukumar Jonathan Wei Bao Chua Dat T Nguyen Toan Q Nguyen Lina Hsiu Kim Lim Amaury Cazenave-Gassiot Long N Nguyen Source Type: research

The senescent mesothelial matrix accentuates colonization by ovarian cancer cells
Cell Mol Life Sci. 2023 Dec 3;81(1):2. doi: 10.1007/s00018-023-05017-x.ABSTRACTOvarian cancer is amongst the most morbid of gynecological malignancies due to its diagnosis at an advanced stage, a transcoelomic mode of metastasis, and rapid transition to chemotherapeutic resistance. Like all other malignancies, the progression of ovarian cancer may be interpreted as an emergent outcome of the conflict between metastasizing cancer cells and the natural defense mounted by microenvironmental barriers to such migration. Here, we asked whether senescence in coelom-lining mesothelia, brought about by drug exposure, affects their ...
Source: Cellular and Molecular Life Sciences : CMLS - December 3, 2023 Category: Cytology Authors: Bharat Vivan Thapa Mallar Banerjee Tilmann Glimm Deepak K Saini Ramray Bhat Source Type: research

CCDC146 is required for sperm flagellum biogenesis and male fertility in mice
Cell Mol Life Sci. 2023 Dec 1;81(1):1. doi: 10.1007/s00018-023-05025-x.ABSTRACTMultiple morphological abnormalities of the flagella (MMAF) is a severe disease of male infertility, while the pathogenetic mechanisms of MMAF are still incompletely understood. Previously, we found that the deficiency of Ccdc38 might be associated with MMAF. To understand the underlying mechanism of this disease, we identified the potential partner of this protein and found that the coiled-coil domain containing 146 (CCDC146) can interact with CCDC38. It is predominantly expressed in the testes, and the knockout of this gene resulted in complet...
Source: Cellular and Molecular Life Sciences : CMLS - December 1, 2023 Category: Cytology Authors: Yanjie Ma Bingbing Wu Yinghong Chen Shuang Ma Liying Wang Tingting Han Xiaolei Lin Fulin Yang Chao Liu Jianguo Zhao Wei Li Source Type: research

Molecular modeling of apoE in complexes with Alzheimer's amyloid- β fibrils from human brain suggests a structural basis for apolipoprotein co-deposition with amyloids
Cell Mol Life Sci. 2023 Nov 27;80(12):376. doi: 10.1007/s00018-023-05026-w.ABSTRACTApolipoproteins co-deposit with amyloids, yet apolipoprotein-amyloid interactions are enigmatic. To understand how apoE interacts with Alzheimer's amyloid-β (Aβ) peptide in fibrillary deposits, the NMR structure of full-length human apoE was docked to four structures of patient-derived Aβ1-40 and Aβ1-42 fibrils determined previously using cryo-electron microscopy or solid-state NMR. Similar docking was done using the NMR structure of human apoC-III. In all complexes, conformational changes in apolipoproteins were required to expose large...
Source: Cellular and Molecular Life Sciences : CMLS - November 27, 2023 Category: Cytology Authors: Emily Lewkowicz Mari N Nakamura Michael J Rynkiewicz Olga Gursky Source Type: research

Disruption of cholangiocyte-B cell crosstalk by blocking the CXCL12-CXCR4 axis alleviates liver fibrosis
Cell Mol Life Sci. 2023 Nov 27;80(12):379. doi: 10.1007/s00018-023-05032-y.ABSTRACTB cells can promote liver fibrosis, but the mechanism of B cell infiltration and therapy against culprit B cells are lacking. We postulated that the disruption of cholangiocyte-B-cell crosstalk could attenuate liver fibrosis by blocking the CXCL12-CXCR4 axis via a cyclooxygenase-2-independent effect of celecoxib. In wild-type mice subjected to thioacetamide, celecoxib ameliorated lymphocytic infiltration and liver fibrosis. By single-cell RNA sequencing and flow cytometry, CXCR4 was established as a marker for profibrotic and liver-homing ph...
Source: Cellular and Molecular Life Sciences : CMLS - November 27, 2023 Category: Cytology Authors: Linhao Zhang Chong Zhao Wenting Dai Huan Tong Wenjuan Yang Zhiyin Huang Chengwei Tang Jinhang Gao Source Type: research