Pub Date : 2024-09-30DOI: 10.1152/ajpcell.00553.2024
Wayne X Du, Craig A Goodman, Paul Gregorevic
Ubiquitination is a post-translational modification that plays important roles in regulating protein stability, function, localization, and protein-protein interactions. Proteins are ubiquitinated via a process involving specific E1 activating enzymes, E2 conjugating enzymes, and E3 ligases. Simultaneously, protein ubiquitination is opposed by deubiquitinating enzymes (DUBs). DUB-mediated deubiquitination can change protein function or fate and recycle ubiquitin to maintain the free ubiquitin pool. Approximately 100 DUBs have been identified in the mammalian genome, and characterized into seven classes (USP, OTU, UCH, MJD, JAMM, MINDY and ZUP classes). Of these 100 DUBs, there has only been relatively limited investigation of 19 specifically in skeletal muscle cells, in vitro or in vivo, using overexpression, knockdown, and knockout models. To date, evidence indicates roles for individual DUBs in regulating aspects of myogenesis, protein turnover, muscle mass, and muscle metabolism. However, the exact mechanism by which these DUBs act (i.e. the specific targets of these DUBs and the type of ubiquitin chains they target) is still largely unknown, underscoring how little we know about DUBs in skeletal muscle. This review endeavors to comprehensively summarize the current state of knowledge of the function of DUBs in skeletal muscle and highlight the opportunities for gaining a greater understanding through further research into this important area of skeletal muscle and ubiquitin biology.
{"title":"Deubiquitinases in skeletal muscle - The Underappreciated Side of the Ubiquitination Coin.","authors":"Wayne X Du, Craig A Goodman, Paul Gregorevic","doi":"10.1152/ajpcell.00553.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00553.2024","url":null,"abstract":"<p><p>Ubiquitination is a post-translational modification that plays important roles in regulating protein stability, function, localization, and protein-protein interactions. Proteins are ubiquitinated <i>via</i> a process involving specific E1 activating enzymes, E2 conjugating enzymes, and E3 ligases. Simultaneously, protein ubiquitination is opposed by deubiquitinating enzymes (DUBs). DUB-mediated deubiquitination can change protein function or fate and recycle ubiquitin to maintain the free ubiquitin pool. Approximately 100 DUBs have been identified in the mammalian genome, and characterized into seven classes (USP, OTU, UCH, MJD, JAMM, MINDY and ZUP classes). Of these 100 DUBs, there has only been relatively limited investigation of 19 specifically in skeletal muscle cells, <i>in vitro</i> or <i>in vivo,</i> using overexpression, knockdown, and knockout models. To date, evidence indicates roles for individual DUBs in regulating aspects of myogenesis, protein turnover, muscle mass, and muscle metabolism. However, the exact mechanism by which these DUBs act (i.e. the specific targets of these DUBs and the type of ubiquitin chains they target) is still largely unknown, underscoring how little we know about DUBs in skeletal muscle. This review endeavors to comprehensively summarize the current state of knowledge of the function of DUBs in skeletal muscle and highlight the opportunities for gaining a greater understanding through further research into this important area of skeletal muscle and ubiquitin biology.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339322","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}
Pub Date : 2024-09-23DOI: 10.1152/ajpcell.00457.2024
Chao Zhang, Shuai Wu
This study investigates the role of the long non-coding RNA (lncRNA) ZNF197-AS1 in uveal melanoma (UM), focusing on its function within a competing endogenous RNA (ceRNA) network. Utilizing the UM-related TCGA dataset, we analyzed the expression levels of ZNF197-AS1 and its correlation with miR-425 and GABARAPL1, an essential autophagy-related gene. Our analysis revealed that ZNF197-AS1 acts as a ceRNA by competitively binding to miR-425, resulting in the upregulation of GABARAPL1. This interaction plays a crucial role in the growth and metastasis of UM. The expression of GABARAPL1 showed a strong correlation with the clinical outcomes of UM patients. Furthermore, in vitro assays confirmed that ZNF197-AS1 impedes UM cell proliferation, migration, and invasion by modulating the miR-425/GABARAPL1 axis. These findings suggest that ZNF197-AS1 can effectively inhibit UM progression through this ceRNA regulatory network. This study provides valuable insights into the molecular mechanisms underlying UM and highlights the potential of targeting the ZNF197-AS1/miR-425/GABARAPL1 axis as a therapeutic strategy for UM.
本研究调查了长非编码 RNA(lncRNA)ZNF197-AS1 在葡萄膜黑色素瘤(UM)中的作用,重点研究了它在竞争性内源性 RNA(ceRNA)网络中的功能。利用 UM 相关的 TCGA 数据集,我们分析了 ZNF197-AS1 的表达水平及其与 miR-425 和 GABARAPL1(一种重要的自噬相关基因)的相关性。我们的分析表明,ZNF197-AS1 通过与 miR-425 竞争性结合,起到了 ceRNA 的作用,从而导致 GABARAPL1 的上调。这种相互作用在 UM 的生长和转移中起着至关重要的作用。GABARAPL1 的表达与 UM 患者的临床预后密切相关。此外,体外实验证实 ZNF197-AS1 通过调节 miR-425/GABARAPL1 轴阻碍了 UM 细胞的增殖、迁移和侵袭。这些发现表明,ZNF197-AS1 可通过这一 ceRNA 调控网络有效抑制 UM 的发展。这项研究为研究UM的分子机制提供了有价值的见解,并凸显了靶向ZNF197-AS1/miR-425/GABARAPL1轴作为UM治疗策略的潜力。
{"title":"ZNF197-AS1/miR-425/GABARAPL1 Axis: A Novel Regulatory Mechanism in Uveal Melanoma.","authors":"Chao Zhang, Shuai Wu","doi":"10.1152/ajpcell.00457.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00457.2024","url":null,"abstract":"<p><p>This study investigates the role of the long non-coding RNA (lncRNA) <i>ZNF197-AS1</i> in uveal melanoma (UM), focusing on its function within a competing endogenous RNA (ceRNA) network. Utilizing the UM-related TCGA dataset, we analyzed the expression levels of <i>ZNF197-AS1</i> and its correlation with <i>miR-425</i> and <i>GABARAPL1</i>, an essential autophagy-related gene. Our analysis revealed that <i>ZNF197-AS1</i> acts as a ceRNA by competitively binding to <i>miR-425</i>, resulting in the upregulation of <i>GABARAPL1</i>. This interaction plays a crucial role in the growth and metastasis of UM. The expression of <i>GABARAPL1</i> showed a strong correlation with the clinical outcomes of UM patients. Furthermore, <i>in vitro</i> assays confirmed that <i>ZNF197-AS1</i> impedes UM cell proliferation, migration, and invasion by modulating the <i>miR-425/GABARAPL1</i> axis. These findings suggest that ZNF197-AS1 can effectively inhibit UM progression through this ceRNA regulatory network. This study provides valuable insights into the molecular mechanisms underlying UM and highlights the potential of targeting the <i>ZNF197-AS1/miR-425/GABARAPL1</i> axis as a therapeutic strategy for UM.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279083","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}
Pub Date : 2024-09-16DOI: 10.1152/ajpcell.00094.2024
Sarannya Edamana, Frédéric H. Login, Andreas Riishede, Vibeke S. Dam, Teresa Kirkegaard, Lene N. Nejsum
American Journal of Physiology-Cell Physiology, Ahead of Print.
美国生理学-细胞生理学杂志》,提前出版。
{"title":"The water channels Aquaporin-1 and Aquaporin-3 interact with and affect the cell polarity protein Scribble in 3D in vitro models of breast cancer","authors":"Sarannya Edamana, Frédéric H. Login, Andreas Riishede, Vibeke S. Dam, Teresa Kirkegaard, Lene N. Nejsum","doi":"10.1152/ajpcell.00094.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00094.2024","url":null,"abstract":"American Journal of Physiology-Cell Physiology, Ahead of Print. <br/>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":"119 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266490","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}
Pub Date : 2024-09-16DOI: 10.1152/ajpcell.00413.2024
Tomislav Smoljo, Hrvoje Lalic, Vilma Dembitz, Barbara Tomic, Josip Batinic, Radovan Vrhovac, Antonio Bedalov, Dora Visnjic
American Journal of Physiology-Cell Physiology, Ahead of Print.
美国生理学-细胞生理学杂志》,提前出版。
{"title":"Bone Marrow Stromal Cells Enhance Differentiation of Acute Myeloid Leukemia Induced by Pyrimidine Synthesis Inhibitors","authors":"Tomislav Smoljo, Hrvoje Lalic, Vilma Dembitz, Barbara Tomic, Josip Batinic, Radovan Vrhovac, Antonio Bedalov, Dora Visnjic","doi":"10.1152/ajpcell.00413.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00413.2024","url":null,"abstract":"American Journal of Physiology-Cell Physiology, Ahead of Print. <br/>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":"99 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266489","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}
Pub Date : 2024-09-09DOI: 10.1152/ajpcell.00564.2023
Ting Liu, Jialing Yuan, Caihong Dai, Mystie X Chen, Jerry Fan, Benjamin D. Humphreys, David J. Fulton, Daniel T. Kleven, Xingjun Fan, Zheng Dong, Jian-Kang Chen
American Journal of Physiology-Cell Physiology, Ahead of Print.
美国生理学-细胞生理学杂志》,提前出版。
{"title":"Pik3c3 Expression Profiling in the Mouse Kidney and Its Role in Proximal Tubule Cell Physiology","authors":"Ting Liu, Jialing Yuan, Caihong Dai, Mystie X Chen, Jerry Fan, Benjamin D. Humphreys, David J. Fulton, Daniel T. Kleven, Xingjun Fan, Zheng Dong, Jian-Kang Chen","doi":"10.1152/ajpcell.00564.2023","DOIUrl":"https://doi.org/10.1152/ajpcell.00564.2023","url":null,"abstract":"American Journal of Physiology-Cell Physiology, Ahead of Print. <br/>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":"4 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142204166","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":"Corrigendum for Hagen et al., volume 327, 2024, p. C372–C378","authors":"","doi":"10.1152/ajpcell.00326.2024_cor","DOIUrl":"https://doi.org/10.1152/ajpcell.00326.2024_cor","url":null,"abstract":"American Journal of Physiology-Cell Physiology, Volume 327, Issue 3, Page C867-C867, September 2024. <br/>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":"14 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142204250","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}
Pub Date : 2024-09-01Epub Date: 2024-07-09DOI: 10.1152/ajpcell.00327.2024
Brandon N VanderVeen, Thomas D Cardaci, Brooke M Bullard, Michael Madden, Jie Li, Kandy T Velazquez, Jason L Kubinak, Daping Fan, E Angela Murphy
Cancer cachexia, or the unintentional loss of body weight in patients with cancer, is a multiorgan and multifactorial syndrome with a complex and largely unknown etiology; however, metabolic dysfunction and inflammation remain hallmarks of cancer-associated wasting. Although cachexia manifests with muscle and adipose tissue loss, perturbations to the gastrointestinal tract may serve as the frontline for both impaired nutrient absorption and immune-activating gut dysbiosis. Investigations into the gut microbiota have exploded within the past two decades, demonstrating multiple gut-tissue axes; however, the link between adipose and skeletal muscle wasting and the gut microbiota with cancer is only beginning to be understood. Furthermore, the most used anticancer drugs (e.g. chemotherapy and immune checkpoint inhibitors) negatively impact gut homeostasis, potentially exacerbating wasting and contributing to poor patient outcomes and survival. In this review, we 1) highlight our current understanding of the microbial changes that occur with cachexia, 2) discuss how microbial changes may contribute to adipose and skeletal muscle wasting, and 3) outline study design considerations needed when examining the role of the microbiota in cancer-induced cachexia.
{"title":"Involvement of the gut microbiota in cancer cachexia.","authors":"Brandon N VanderVeen, Thomas D Cardaci, Brooke M Bullard, Michael Madden, Jie Li, Kandy T Velazquez, Jason L Kubinak, Daping Fan, E Angela Murphy","doi":"10.1152/ajpcell.00327.2024","DOIUrl":"10.1152/ajpcell.00327.2024","url":null,"abstract":"<p><p>Cancer cachexia, or the unintentional loss of body weight in patients with cancer, is a multiorgan and multifactorial syndrome with a complex and largely unknown etiology; however, metabolic dysfunction and inflammation remain hallmarks of cancer-associated wasting. Although cachexia manifests with muscle and adipose tissue loss, perturbations to the gastrointestinal tract may serve as the frontline for both impaired nutrient absorption and immune-activating gut dysbiosis. Investigations into the gut microbiota have exploded within the past two decades, demonstrating multiple gut-tissue axes; however, the link between adipose and skeletal muscle wasting and the gut microbiota with cancer is only beginning to be understood. Furthermore, the most used anticancer drugs (e.g. chemotherapy and immune checkpoint inhibitors) negatively impact gut homeostasis, potentially exacerbating wasting and contributing to poor patient outcomes and survival. In this review, we <i>1</i>) highlight our current understanding of the microbial changes that occur with cachexia, <i>2</i>) discuss how microbial changes may contribute to adipose and skeletal muscle wasting, and <i>3</i>) outline study design considerations needed when examining the role of the microbiota in cancer-induced cachexia.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C661-C670"},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562429","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}