{"title":"Targeting HPV for the prevention, diagnosis, and treatment of Cervical Cancer.","authors":"Huiling Ni, Canhua Huang, Zhi Ran, Shan Li, Chunmei Kuang, Yu Zhang, Kai Yuan","doi":"10.1093/jmcb/mjae046","DOIUrl":"https://doi.org/10.1093/jmcb/mjae046","url":null,"abstract":"<p><p>Despite advances in screening and prevention, cervical cancer (CC) remains an unresolved public health issue and poses a significant global challenge, particularly for women in low-income regions. Human papillomavirus (HPV) infection, especially with the high-risk strains, is a primary driver of cervical carcinogenesis. Emerging evidence indicates that integrating HPV testing with existing approaches, such as cervical cytology and visual inspection, offers enhanced sensitivity and specificity in CC screening. HPV infection-associated biomarkers, including HPV E6/E7 oncogenes, p16^INK4a, DNA methylation signatures, and non-coding RNAs, offer valuable insights into disease progression and the development of personalized interventions. Preventive and therapeutic vaccination against HPV, along with tertiary prevention strategies such as the use of antiviral and immune-modulating drugs for HPV-related lesions, show great clinical potential. At the mechanistic level, single-cell RNA sequencing analysis and the development of organoid models for HPV infection provide new cellular and molecular insights into HPV-related CC pathogenesis. This review focuses on the crucial roles of HPV in the prevention, diagnosis, and treatment of CC, with particular emphasis on the latest advancements in screening and disease intervention.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cohesin ring gates are specialized for meiotic cell division.","authors":"Yuanyuan Liu, Bohan Liu, Ruirui Zhang, Zixuan Zhu, Li Zhao, Ruijie Jiang, Yinghao Wang, Feifei Qi, Ruoxi Wang, Huijie Zhao, Jun Zhou, Jinmin Gao","doi":"10.1093/jmcb/mjae047","DOIUrl":"https://doi.org/10.1093/jmcb/mjae047","url":null,"abstract":"<p><p>Cohesin is a ring complex closed with SMC-1, SMC-3, and a kleisin subunit, mediating sister chromatid cohesion in mitosis and meiosis. Kleisin N- and C-terminal domains interact with SMC-3 and SMC-1, forming two distinct cohesin gates. Whether these gates are specialized for mitosis and meiosis remains elusive. Here, we create Caenorhabditis elegans mutants that express chimeric proteins swapping N- and C-terminal domains between different kleisins to investigate how these gates are specialized for different cell division programs. Replacing the meiotic REC-8 N-terminus with that of a cell division-unrelated kleisin COH-1 or the mitotic kleisin SCC-1 disrupts inter-sister chromatid cohesion and causes severe meiotic defects. Swapping the REC-8 C-terminus with that of COH-1 or SCC-1 largely retains the meiotic functions of REC-8 but causes age-related chromosome abnormalities. A specialized C-terminus is also required for the functions of SCC-1. Furthermore, point mutations in REC-8 C-terminus cause severe meiotic defects without impairing SMC-1-kleisin interaction, suggesting an integrated SMC-1-kleisin gate. These findings suggest the requirements for specialized cohesin gates in different biological processes.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jihyun Jang, Mette Bentsen, Jin Bu, Ling Chen, Alexandre Rosa Campos, Mario Looso, Deqiang Li
{"title":"HDAC7 promotes cardiomyocyte proliferation by suppressing Myocyte Enhancer Factor 2.","authors":"Jihyun Jang, Mette Bentsen, Jin Bu, Ling Chen, Alexandre Rosa Campos, Mario Looso, Deqiang Li","doi":"10.1093/jmcb/mjae044","DOIUrl":"https://doi.org/10.1093/jmcb/mjae044","url":null,"abstract":"<p><p>Postnatal mammalian cardiomyocytes (CMs) rapidly lose proliferative capacity and exit the cell cycle and undergo further differentiation and maturation. Cell cycle activation has been a major strategy to stimulate postnatal CM proliferation, albeit achieving modest effects. One impediment is that postnatal CMs may need to undergo dedifferentiation before proliferation, if not simultaneously. Here, we report that overexpression of Hdac7 in neonatal mouse CMs results in significant CM dedifferentiation and proliferation. Mechanistically, we show that HDAC7-mediated CM proliferation is contingent on dedifferentiation, which is accomplished through suppressing MEF2. Hdac7 overexpression in CM shifts the chromatin state from binding MEF2, which favors the differentiation transcriptional program to AP-1, which favors the proliferative transcriptional program. Further, we found that HDAC7 interacts with minichromosome maintenance complex (MCM) components to initiate cell cycle progression. Our findings reveal that HDAC7 promotes CM proliferation by its dual action on CM dedifferentiation and proliferation, uncovering a potential new strategy for heart regeneration/repair.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenya Yu, Xiang Liu, Hong Chen, Jiahe Tian, Meina Li, Wei Mu, Yang Ge
{"title":"Gender differences in the health workforce in China: an analysis of national data.","authors":"Wenya Yu, Xiang Liu, Hong Chen, Jiahe Tian, Meina Li, Wei Mu, Yang Ge","doi":"10.1093/jmcb/mjae040","DOIUrl":"https://doi.org/10.1093/jmcb/mjae040","url":null,"abstract":"<p><p>Gender differences in the health workforce matter for women's health and healthcare, and is also crucial for both health and economic development. Drawing on limited national gender data from China over the last 10 years, during which the country was undergoing a healthcare reform, this study dissects gender-related issues to identify existing problems, monitor progress, and develop strategies to promote change. Although women constituted the majority of health workers, they are predominantly engaged in service-oriented occupations. The gender distribution substantially differed between urban and rural primary health institutions. Moreover, significant differences in gender distribution among professional public health institutions were observed. The gender distribution of administrators varied in different types of health institutions. Women had lighter workloads because of the imbalanced distribution of specialties. Academicians comprised very few female scientists. To promote a more balanced gender distribution, policies should be developed to encourage a more reasonable division of family responsibilities. Further, equal higher education opportunities should be ensured for girls, especially in rural areas. Solutions to free more women from work-marriage-childcare conflicts and to decrease turnover rates deserve further discussion. Gender data should be highlighted and optimized to further advance gender differences among the health workforce and for women's health in China.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jianyu Yang, Fulin Xing, Fen Hu, Mengdi Hou, Hao Dong, Jiayu Cheng, Wan Li, Rui Yan, Jingjun Xu, Ke Xu, Leiting Pan
{"title":"Super-resolution microscopy unveils the nanoscale organization and self-limiting clustering of CD47 in human erythrocytes.","authors":"Jianyu Yang, Fulin Xing, Fen Hu, Mengdi Hou, Hao Dong, Jiayu Cheng, Wan Li, Rui Yan, Jingjun Xu, Ke Xu, Leiting Pan","doi":"10.1093/jmcb/mjae041","DOIUrl":"https://doi.org/10.1093/jmcb/mjae041","url":null,"abstract":"<p><p>The transmembrane protein CD47, an innate immune checkpoint protein, plays a pivotal role in preventing healthy erythrocytes from immune clearance. Our study utilized stochastic optical-reconstruction microscopy (STORM) and single-molecule analysis to investigate the distribution of CD47 on the human erythrocyte membrane. Contrary to previous findings in mouse erythrocytes, we discovered that CD47 exists in randomly distributed monomers rather than in clusters across the human erythrocyte membrane. Using 2nd antibody-induced crosslinking, we found that CD47 aggregates into stable clusters within minutes. By comparing these STORM results with those of the fully mobile protein CD59 and the cytoskeleton-bound membrane protein glycophorin C under similar conditions, as well as devising two-color STORM co-labeling and co-clustering experiments, we further quantitatively revealed an intermediate, self-limiting clustering behavior of CD47, elucidating its fractional (∼14%) attachment to the cytoskeleton. Moreover, we report reductions in both the amount of CD47 and its clustering capability in aged erythrocytes, providing new insight into erythrocyte senescence. Together, the combination of STORM and 2nd antibody-based crosslinking unveils the unique self-limiting clustering behavior of CD47 due to its fractional cytoskeleton attachment.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hypoxia signaling in the adipose tissue.","authors":"Phu M Huynh, Fenfen Wang, Yu A An","doi":"10.1093/jmcb/mjae039","DOIUrl":"https://doi.org/10.1093/jmcb/mjae039","url":null,"abstract":"<p><p>Obesity per se is rapidly emerging all over the planet and further accounts for many other life-threatening conditions, such as diabetes, cardiovascular diseases, and cancers. Decreased oxygen supply or increased relative oxygen consumption in the adipose tissue results in adipose tissue hypoxia, which is a hallmark of obesity. This review aims to provide an up-to-date overview of the hypoxia signaling in the adipose tissue. First, we summarize literature evidence to demonstrate that hypoxia is regularly observed during adipose tissue remodeling in human and rodent models of obesity. Next, we discuss how hypoxia-inducible factors (HIFs) are regulated and how adipose tissues behave in response to hypoxia. Then, the differential roles of adipose HIF-1α and HIF-2α in adipose tissue biology and obesity pathology are highlighted. Finally, the review emphasizes the importance of modulating adipose hypoxia as a therapeutic avenue to assist adipose tissues in functionally adapting to hypoxic conditions, ultimately promoting adipose health and improving outcomes due to obesity.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cyrine Bentaleb, Souad Adrouche, Jade Finkelstein, Christelle Devisme, Nathalie Callens, Claude Capron, Morgane Bomsel, Fernando Real
{"title":"HIV-1 inhibits IFITM3 expression to promote the infection of megakaryocytes.","authors":"Cyrine Bentaleb, Souad Adrouche, Jade Finkelstein, Christelle Devisme, Nathalie Callens, Claude Capron, Morgane Bomsel, Fernando Real","doi":"10.1093/jmcb/mjae042","DOIUrl":"https://doi.org/10.1093/jmcb/mjae042","url":null,"abstract":"<p><p>Despite an undetectable plasma viral load as a result of antiretroviral therapy, HIV-1-infected individuals with poor immune reconstitution harbor infectious HIV-1 within their platelets. Megakaryocytes, as platelet precursors, are the likely cellular origin of these HIV-1-containing platelets. To investigate the mechanisms that allow megakaryocytes to support HIV-1 infection, we established in vitro models of viral infection using hematopoietic stem cell-derived megakaryocytes and the megakaryocytic MEG-01 cell line. We observed HIV-1 DNA provirus integration into the megakaryocyte cell genome, self-limiting virus production, and HIV-1 protein and RNA compartmentalization, which are hallmarks of HIV-1 infection in myeloid cells. In addition, following HIV-1 infection of megakaryocyte precursors, the expression of interferon-induced transmembrane protein 3 (IFITM3), an antiviral factor constitutively expressed in megakaryocytes, was inhibited in terminally differentiated HIV-1-infected megakaryocytes. IFITM3 knockdown in MEG-01 cells prior to infection led to enhanced HIV-1 infection, indicating that IFITM3 acts as an HIV-1 restriction factor in megakaryocytes. Together, these findings indicate that megakaryocyte precursors are susceptible to HIV-1 infection, leading to terminally differentiated megakaryocytes harboring virus in a process regulated by IFITM3. Megakaryocytes may thus constitute a neglected HIV-1 reservoir that warrants further study in order to develop improved antiretroviral therapies and to facilitate HIV-1 eradication.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yueling Zhu, Shiyan Lin, Lingshen Meng, Min Sun, Maili Liu, Jingyuan Li, Chun Tang, Zhou Gong
{"title":"ATP promotes protein coacervation through conformational compaction.","authors":"Yueling Zhu, Shiyan Lin, Lingshen Meng, Min Sun, Maili Liu, Jingyuan Li, Chun Tang, Zhou Gong","doi":"10.1093/jmcb/mjae038","DOIUrl":"https://doi.org/10.1093/jmcb/mjae038","url":null,"abstract":"<p><p>ATP has been recognized as a hydrotrope in the phase separation process of intrinsically disordered proteins (IDPs). Surprisingly, when using the disordered RG/RGG-rich motif from HNRNPG protein as a model system, we discover a biphasic relationship between the ATP concentration and IDP phase separation. We show that at a relatively low ATP concentration, ATP dynamically interacts with the IDP, which neutralizes protein surface charges, promotes intermolecular interactions, and consequently promotes phase separation. We further demonstrate that ATP induces a compact conformation of the IDP, accounting for the reduced solvent exchange rate and lower compression ratio during phase separation. As ATP concentration increases, its hydrotropic properties emerge, leading to the dissolution of the phase-separated droplets. Our finding uncovers a complex mechanism by which ATP molecules modulate the structure, interaction, and phase separation of IDPs, and accounts for the distinct phase separation behaviors for the charge-rich RGG motif and other low-complexity IDPs.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuhan Lou, Litao Wu, Wanlin Cai, Huan Deng, Rong Sang, Shanshan Xie, Xiao Xu, Xin Yuan, Cheng Wu, Man Xu, Wanzhong Ge, Yongmei Xi, Xiaohang Yang
{"title":"The FAcilitates Chromatin Transcription complex regulates the ratio of glycolysis to oxidative phosphorylation in neural stem cells.","authors":"Yuhan Lou, Litao Wu, Wanlin Cai, Huan Deng, Rong Sang, Shanshan Xie, Xiao Xu, Xin Yuan, Cheng Wu, Man Xu, Wanzhong Ge, Yongmei Xi, Xiaohang Yang","doi":"10.1093/jmcb/mjae017","DOIUrl":"10.1093/jmcb/mjae017","url":null,"abstract":"<p><p>Defects in the FAcilitates Chromatin Transcription (FACT) complex, a histone chaperone composed of SSRP1 and SUPT16H, are implicated in intellectual disability. Here, we reveal that the FACT complex promotes glycolysis and sustains the correct cell fate of neural stem cells/neuroblasts in the Drosophila 3rd instar larval central brain. We show that the FACT complex binds to the promoter region of the estrogen-related receptor (ERR) gene and positively regulates ERR expression. ERR is known to act as an aerobic glycolytic switch by upregulating the enzymes required for glycolysis. Dysfunction of the FACT complex leads to the downregulation of ERR transcription, resulting in a decreased ratio of glycolysis to oxidative phosphorylation (G/O) in neuroblasts. Consequently, neuroblasts exhibit smaller cell sizes, lower proliferation potential, and altered cell fates. Overexpression of ERR or suppression of mitochondrial oxidative phosphorylation in neuroblasts increases the relative G/O ratio and rescues defective phenotypes caused by dysfunction of the FACT complex. Thus, the G/O ratio, mediated by the FACT complex, plays a crucial role in neuroblast cell fate maintenance. Our study may shed light on the mechanism by which mutations in the FACT complex lead to intellectual disability in humans.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synergistic regulation of fusion pore opening and dilation by SNARE and synaptotagmin-1.","authors":"Kaiju Li, Kaiyu Li, Jiaqi Fan, Xing Zhang, Chengyan Tao, Yijuan Xiang, Lele Cui, Hao Li, Minghan Li, Yanjing Zhang, Jia Geng, Ying Lai","doi":"10.1093/jmcb/mjae011","DOIUrl":"10.1093/jmcb/mjae011","url":null,"abstract":"<p><p>Fusion pore opening is a transient intermediate state of synaptic vesicle exocytosis, which is highly dynamic and precisely regulated by the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex and synaptotagmin-1 (Syt1). Yet, the regulatory mechanism is not fully understood. In this work, using single-channel membrane fusion electrophysiology, we determined that SNAREpins are important for driving fusion pore opening and dilation but incapable of regulating the dynamics. When Syt1 was added, the closing frequency of fusion pores significantly increased, while the radius of fusion pores mildly decreased. In response to Ca2+, SNARE/Syt1 greatly increased the radius of fusion pores and reduced their closing frequency. Moreover, the residue F349 in the C2B domain of Syt1, which mediates Syt1 oligomerization, was required for clamping fusion pore opening in the absence of Ca2+, probably by extending the distance between the two membranes. Finally, in Ca2+-triggered fusion, the primary interface between SNARE and Syt1 plays a critical role in stabilizing and dilating the fusion pore, while the polybasic region of Syt1 C2B domain has a mild effect on increasing the radius of the fusion pore. In summary, our results suggest that Syt1, SNARE, and the anionic membrane synergically orchestrate the dynamics of fusion pore opening in synaptic vesicle exocytosis.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}