Ilaria Frasson, Linda Diamante, Manuela Zangrossi, Elena Carbognin, Anna Dalla Pietà, Alessandro Penna, Antonio Rosato, Ranieri Verin, Filippo Torrigiani, Cristiano Salata, Marìa Paula Dizanzo, Lorenzo Vaccaro, Davide Cacchiarelli, Sara N Richter, Marco Montagner, Graziano Martello
The high mutation rate of SARS-CoV-2 leads to the emergence of multiple variants, some of which are resistant to vaccines and drugs targeting viral elements. Targeting host dependency factors, e.g. cellular proteins required for viral replication, would help prevent resistance. However, it remains unclear whether different SARS-CoV-2 variants induce conserved cellular responses and exploit the same core host factors. To this end, we compared three variants of concern and found that the host transcriptional response was conserved, differing only in kinetics and magnitude...
February 1, 2024: Journal of Molecular Cell Biology
Peter Zorn, Jaime Calvo Sánchez, Tala Alakhras, Barbara Schreier, Michael Gekle, Stefan Hüttelmaier, Marcel Köhn
Alternative splicing is one of the major cellular processes that determine the tissue-specific expression of protein variants. However, it remains challenging to identify physiologically relevant and tissue-selective proteins that are generated by alternative splicing. Hence, we investigated the target spectrum of the splicing factor Rbfox1 in the cardiac muscle context in more detail. By using a combination of in silico target prediction and in cell validation, we identified several focal adhesion proteins as alternative splicing targets of Rbfox1...
January 22, 2024: Journal of Molecular Cell Biology
Yang Li, Qiang Sun, Zhi Yang, Gang Yuan
No abstract text is available yet for this article.
January 12, 2024: Journal of Molecular Cell Biology
Wei Liu, Zhen Dou, Chunyue Wang, Gangyin Zhao, Fengge Wu, Chunli Wang, Felix Aikhionbare, Mingliang Ye, Divine Mensah Sedzro, Zhenye Yang, Chuanhai Fu, Zhikai Wang, Xinjiao Gao, Xuebiao Yao, Xiaoyu Song, Xing Liu
Accurate chromosome segregation in mitosis depends on kinetochores that connect centromeric chromatin to spindle microtubules. Centromeres are captured by individual microtubules via a kinetochore constitutive centromere-associated network (CCAN) during chromosome segregation. CCAN contains 16 subunits, including CENP-W and CENP-T. However, the molecular recognition and mitotic regulation of the CCAN assembly remain elusive. Here, we revealed that CENP-W binds to the histone fold domain and an uncharacterized N-terminal region of CENP-T...
January 10, 2024: Journal of Molecular Cell Biology
Xiaozhen Song, Ruixing Hu, Yi Chen, Man Xiao, Hong Zhang, Shengnan Wu, Qing Lu
TRAF7 serves as a crucial intracellular adaptor and E3 ubiquitin ligase involved in signal transduction pathways, contributing to immune responses, tumor progression, and embryonic development. Somatic mutations within the coiled-coil (CC) domain and WD40 repeat domain of TRAF7 could cause brain tumors, while germline pathogenic mutations contribute to severe developmental abnormalities. However, the precise molecular mechanism underlying TRAF7 involvement in embryonic development remains unclear. In this study, we employed zebrafish as an in-vivo model system...
January 4, 2024: Journal of Molecular Cell Biology
Han Yao, Meng Zhang, Donglai Wang
This year marks the fourth decade of research into the protein SET, which was discovered in 1992. SET was initially identified as an oncoprotein, but later, it was shown to be a multifaceted protein involved in regulating numerous biological processes under both physiological and pathophysiological conditions. SET dysfunction is closely associated with diseases, such as cancer and Alzheimer's disease. With the increasing understanding of how SET works and how it is regulated in cells, targeting aberrant SET has emerged as a potential strategy for disease intervention...
December 29, 2023: Journal of Molecular Cell Biology
Raku Son, Kenji Yamazawa, Akiko Oguchi, Mitsuo Suga, Masaru Tamura, Motoko Yanagita, Yasuhiro Murakawa, Satoshi Kume
The living body is composed of innumerable fine and complex structures. Although these structures have been studied in the past, a vast amount of information pertaining to them still remains unknown. When attempting to observe these ultra-structures, the use of electron microscopy (EM) has become indispensable. However, conventional EM settings are limited to a narrow tissue area, which can bias observations. Recently, new trends in EM research have emerged that provide coverage of far broader, nano-scale fields of view for two-dimensional wide areas and three-dimensional large volumes...
December 26, 2023: Journal of Molecular Cell Biology
Xuxia Ren, Zexu Cui, Qiaoqiao Zhang, Zhiguang Su, Wei Xu, Jinhui Wu, Hao Jiang
Endothelial damage is the initial and crucial factor in the occurrence and development of vascular complications in diabetic patients, contributing to morbidity and mortality. Although hyperglycemia has been identified as a damaging effector, the detailed mechanisms remain elusive. In this study, identified by ATAC-seq and RNA-seq, JunB reverses the inhibition of proliferation and the promotion of apoptosis in human umbilical vein endothelial cells treated with high glucose, mainly through the cell cycle and p53 signaling pathways...
December 22, 2023: Journal of Molecular Cell Biology
Qiyao Liu, Manyun Li, Minli Sun, Ruyue Xin, Yushu Wang, Qin Chen, Xiang Gao, Zhaoyu Lin
Homeostasis of the skin barrier is essential for maintaining normal skin function. Gasdermin A (GSDMA) is highly expressed in the skin and is associated with many skin diseases, such as melanoma and psoriasis. In mice, GSDMA is encoded by three gene homologues, namely Gsdma1, Gsdma2, and Gsdma3. Although Gsdma3 gain-of-function mutations cause hair loss and skin inflammation, Gsdma3-deficient mice show no phenotypes in skin or hair structures. To explore the physiological function of GSDMA, we generated conventional Gsdma1/2/3 knockout (KO) mice...
December 19, 2023: Journal of Molecular Cell Biology
Cheng Chen, Liping Xie, Mingliang Zhang, Shama, Kenneth King Yip Cheng, Weiping Jia
No abstract text is available yet for this article.
December 12, 2023: Journal of Molecular Cell Biology
Te Li, Min Liu, Fan Yu, Song Yang, Weiwen Bu, Kai Liu, Jia Yang, Hua Ni, Mulin Yang, Hanxiao Yin, Renjie Hong, Dengwen Li, Huijie Zhao, Jun Zhou
Carbohydrate metabolism disorders (CMDs), such as diabetes, galactosemia, and mannosidosis, cause ciliopathy-like multiorgan defects. However, the mechanistic link of cilia to CMD complications is still poorly understood. Herein, we describe a significant cilium disassembly upon treatment of cells with pathologically relevant aldoses rather than the corresponding sugar alcohols. Moreover, environmental aldehydes are able to trigger cilium disassembly by the steric hindrance effect of their formyl groups. Mechanistic studies reveal that aldehydes stimulate extracellular calcium influx across the plasma membrane, which subsequently activates the calmodulin-Aurora A-histone deacetylase 6 pathway to deacetylate axonemal microtubules and triggers cilium disassembly...
December 6, 2023: Journal of Molecular Cell Biology
Ting Guo, Chen Miao, Zhonghua Liu, Jingwei Duan, Yanbin Ma, Xiao Zhang, Weiwei Yang, Maoguang Xue, Qiannan Deng, Pengfei Guo, Yongmei Xi, Xiaohang Yang, Xun Huang, Wanzhong Ge
Mutations or dysregulated expression of NF-kappaB activating protein (NKAP) family genes have been found in human cancers. How NKAP family gene mutations promote tumor initiation and progression remains to be determined. Here, we characterized dNKAP, the Drosophila homolog of NKAP, and showed that impaired dNKAP function causes genome instability and tumorigenic growth in a Drosophila epithelial tumor model. dNKAP-knockdown wing imaginal discs exhibit tumorigenic characteristics, including tissue overgrowth, cell invasive behavior, abnormal cell polarity, and cell adhesion defects...
December 6, 2023: Journal of Molecular Cell Biology
Jing Zhang, Shu-Guang Yang, Feng-Quan Zhou
Glycogen synthase kinase 3 (GSK3) signaling plays important and broad roles in regulating neural development in vitro and in vivo. Here, we reviewed recent findings of GSK3-regulated axon regeneration in vivo in both the peripheral and central nervous systems and discussed a few controversial findings in the field. Overall, current evidence indicates that GSK3β signaling serves as an important downstream mediator of the PI3K-AKT pathway to regulate axon regeneration in parallel with the mTORC1 pathway...
December 6, 2023: Journal of Molecular Cell Biology
Siqi Liu, Jia Xu, Yirui Ai, Yunbin Zhang, Shifeng Li, Jinsong Li, Yiping Li
No abstract text is available yet for this article.
December 4, 2023: Journal of Molecular Cell Biology
Hongli Chen, Yuexing Liu, Dan Liu, Yebei Liang, Zhijun Zhu, Keqing Dong, Huating Li, Yuqian Bao, Jiarui Wu, Xuhong Hou, Weiping Jia
Obesity is closely related to non-alcoholic fatty liver disease (NAFLD). Although sex differences in body fat distribution have been well demonstrated, little is known about the sex-specific associations between adipose tissue and the development of NAFLD. Using community-based cohort data, we evaluated the associations between magnetic resonance imaging-quantified areas of abdominal adipose tissue, including visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and incident NAFLD in 2830 participants (1205 males and 1625 females) aged 55-70 years...
November 30, 2023: Journal of Molecular Cell Biology
Ian A Taylor, Ariberto Fassati
Lenacapavir, targeting the HIV-1 capsid, is the first-in-class antiretroviral drug recently approved for clinical use. The development of Lenacapavir is attributed to the remarkable progress in our understanding of the capsid protein made during the last few years. Considered little more than a component of the virus shell to be shed early during infection, capsid has been found to be a key player in the HIV-1 life cycle by interacting with multiple host cell factors, entering the nucleus, and directing integration...
November 30, 2023: Journal of Molecular Cell Biology
Hanwen Zhou, Liyun Yuan, Yuanhu Ju, Yue Hu, Siqi Wang, Ruifang Cao, Zefeng Wang, Guoqing Zhang
No abstract text is available yet for this article.
November 27, 2023: Journal of Molecular Cell Biology
Zhi Zhong, Jiangchuan Du, Xiangjie Zhu, Lingting Guan, Yanyu Hu, Peilin Zhang, Hongyang Wang
Previous studies have shown that hepatocyte-like cells can be generated from fibroblasts using either lineage-specific transcription factors or chemical induction methods. However, these methods have their own deficiencies that restrict the therapeutic applications of such induced hepatocytes. In this study, we present a transgene-free, highly efficient chemical-induced direct reprogramming approach to generate hepatocyte-like cells from mouse embryonic fibroblasts (MEFs). Using a small molecule cocktail (SMC) as an inducer, MEFs can be directly reprogrammed into hepatocyte-like cells, bypassing pluripotent and immature hepatoblast intermediate stages...
November 23, 2023: Journal of Molecular Cell Biology
Fangni Chai, Pan Li, Xin Liu, Zhihui Zhou, Haiyan Ren
As a significant member of the immune checkpoint, programmed cell death 1 ligand 1 (PD-L1) plays a critical role in cancer immune escape and has become an important target for cancer immunotherapy. Clinically approved drugs mainly target the extracellular domain of PD-L1. Recently, the small cytoplasmic domain of PD-L1 has been reported to regulate PD-L1 stability and function through multiple pathways. Therefore, the intracellular domain of PD-L1 and its regulatory pathways could be promising targets for cancer therapy, expanding available strategies for combined immunotherapy...
November 22, 2023: Journal of Molecular Cell Biology
Wukun Ouyang, Qianjin Li, Qiankun Niu, Min Qui, Haian Fu, Yuhong Du, Xiulei Mo
The transforming growth factor-beta (TGFβ) signaling pathway plays crucial roles in the establishment of an immunosuppressive tumor microenvironment, making anti-TGFβ agents a significant area of interest in cancer immunotherapy. However, the clinical translation of current anti-TGFβ agents that target upstream cytokines and receptors remains challenging. Therefore, the development of small-molecule inhibitors specifically targeting SMAD4, the downstream master regulator of the TGFβ pathway, would offer an alternative approach with significant therapeutic potential for anti-TGF-β signaling...
November 15, 2023: Journal of Molecular Cell Biology
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