Advances in biological regulation最新文献

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Steroidogenic Factor-1 form and function: From phospholipids to physiology 类固醇生成因子-1的形式和功能:从磷脂到生理学。
Advances in biological regulation Pub Date : 2024-01-01 DOI: 10.1016/j.jbior.2023.100991
Alexis N. Campbell , Woong Jae Choi , Ethan S. Chi , Abigail R. Orun , James C. Poland , Elizabeth A. Stivison , Jakub N. Kubina , Kimora L. Hudson , Mong Na Claire Loi , Jay N. Bhatia , Joseph W. Gilligan , Adrian A. Quintanà , Raymond D. Blind
{"title":"Steroidogenic Factor-1 form and function: From phospholipids to physiology","authors":"Alexis N. Campbell ,&nbsp;Woong Jae Choi ,&nbsp;Ethan S. Chi ,&nbsp;Abigail R. Orun ,&nbsp;James C. Poland ,&nbsp;Elizabeth A. Stivison ,&nbsp;Jakub N. Kubina ,&nbsp;Kimora L. Hudson ,&nbsp;Mong Na Claire Loi ,&nbsp;Jay N. Bhatia ,&nbsp;Joseph W. Gilligan ,&nbsp;Adrian A. Quintanà ,&nbsp;Raymond D. Blind","doi":"10.1016/j.jbior.2023.100991","DOIUrl":"10.1016/j.jbior.2023.100991","url":null,"abstract":"<div><p>Steroidogenic Factor-1 (SF-1, <em>NR5A1</em>) is a member of the nuclear receptor superfamily of ligand-regulated transcription factors, consisting of a DNA-binding domain (DBD) connected to a transcriptional regulatory ligand binding domain (LBD) via an unstructured hinge domain. SF-1 is a master regulator of development and adult function along the hypothalamic pituitary adrenal and gonadal axes, with strong pathophysiological association with endometriosis and adrenocortical carcinoma. SF-1 was shown to bind and be regulated by phospholipids, one of the most interesting aspects of SF-1 regulation is the manner in which SF-1 interacts with phospholipids: SF-1 buries the phospholipid acyl chains deep in the hydrophobic core of the SF-1 protein, while the lipid headgroups remain solvent-exposed on the exterior of the SF-1 protein surface. Here, we have reviewed several aspects of SF-1 structure, function and physiology, touching on other transcription factors that help regulate SF-1 target genes, non-canonical functions of SF-1, the DNA-binding properties of SF-1, the use of mass spectrometry to identify lipids that associate with SF-1, how protein phosphorylation regulates SF-1 and the structural biology of the phospholipid-ligand binding domain. Together this review summarizes the form and function of Steroidogenic Factor-1 in physiology and in human disease, with particular emphasis on adrenal cancer.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"91 ","pages":"Article 100991"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41099921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Group photo 合影留念。
Advances in biological regulation Pub Date : 2024-01-01 DOI: 10.1016/j.jbior.2024.101018
Lucio Ildebrando Cocco
{"title":"Group photo","authors":"Lucio Ildebrando Cocco","doi":"10.1016/j.jbior.2024.101018","DOIUrl":"10.1016/j.jbior.2024.101018","url":null,"abstract":"","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"91 ","pages":"Article 101018"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S221249262400006X/pdfft?md5=2bbbca000e57ad3231b1f2556f2bb272&pid=1-s2.0-S221249262400006X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Coordinated inositide lipid-phosphatase activities of synaptojanin modulates actin cytoskeleton organization 突触素的肌醇脂磷酸酶协调活动调节肌动蛋白细胞骨架的组织结构
Advances in biological regulation Pub Date : 2024-01-01 DOI: 10.1016/j.jbior.2023.101012
Tong Zhang , Andrew T. Hale , Shuling Guo , John D. York
{"title":"Coordinated inositide lipid-phosphatase activities of synaptojanin modulates actin cytoskeleton organization","authors":"Tong Zhang ,&nbsp;Andrew T. Hale ,&nbsp;Shuling Guo ,&nbsp;John D. York","doi":"10.1016/j.jbior.2023.101012","DOIUrl":"10.1016/j.jbior.2023.101012","url":null,"abstract":"<div><p>Synaptojanin proteins are evolutionarily conserved regulators of vesicle transport and membrane homeostasis. Disruption of synaptojanin function has been implicated in a wide range of neurological disorders. Synaptojanins act as dual-functional lipid phosphatases capable of hydrolyzing a variety of phosphoinositides (PIPs) through autonomous <em>SAC1</em>-like PIP 4-phosphatase and PIP<sub>2</sub> 5-phosphatase domains. The rarity of an evolutionary configuration of tethering two distinct enzyme activities in a single protein prompted us to investigate their individual and combined roles in budding yeast. Both PIP and PIP<sub>2</sub> phosphatase activities are encoded by multiple gene products and are independently essential for cell viability. In contrast, we observed that the synaptojanin proteins utilized both lipid-phosphatase activities to properly coordinate polarized distribution of actin during the cell cycle. Expression of each activity untethered (<em>in trans</em>) failed to properly reconstitute the basal actin regulatory activity; whereas tethering (<em>in cis</em>), even through synthetic linkers, was sufficient to complement these defects. Studies of chimeric proteins harboring PIP and PIP<sub>2</sub> phosphatase domains from a variety of gene products indicate synaptojanin proteins have highly specialized activities and that the length of the linker between the lipid-phosphatase domains is critical for actin regulatory activity. Our data are consistent with synaptojanin possessing a strict requirement for both two-domain configuration for some but not all functions and provide mechanistic insights into a coordinated role of tethering distinct lipid-phosphatase activities.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"91 ","pages":"Article 101012"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212492623000581/pdfft?md5=9765a94c0e2c924c2b070427e61ef1c8&pid=1-s2.0-S2212492623000581-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139456404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deciphering signaling pathways in hematopoietic stem cells: the molecular complexity of Myelodysplastic Syndromes (MDS) and leukemic progression 解密造血干细胞的信号通路:骨髓增生异常综合征(MDS)和白血病进展的分子复杂性。
Advances in biological regulation Pub Date : 2024-01-01 DOI: 10.1016/j.jbior.2024.101014
Irene Casalin , Alessia De Stefano , Eleonora Ceneri , Alessandra Cappellini , Carlo Finelli , Antonio Curti , Stefania Paolini , Sarah Parisi , Letizia Zannoni , Jacqueline Boultwood , James A. McCubrey , Pann-Ghill Suh , Giulia Ramazzotti , Roberta Fiume , Stefano Ratti , Lucia Manzoli , Lucio Cocco , Matilde Y. Follo
{"title":"Deciphering signaling pathways in hematopoietic stem cells: the molecular complexity of Myelodysplastic Syndromes (MDS) and leukemic progression","authors":"Irene Casalin ,&nbsp;Alessia De Stefano ,&nbsp;Eleonora Ceneri ,&nbsp;Alessandra Cappellini ,&nbsp;Carlo Finelli ,&nbsp;Antonio Curti ,&nbsp;Stefania Paolini ,&nbsp;Sarah Parisi ,&nbsp;Letizia Zannoni ,&nbsp;Jacqueline Boultwood ,&nbsp;James A. McCubrey ,&nbsp;Pann-Ghill Suh ,&nbsp;Giulia Ramazzotti ,&nbsp;Roberta Fiume ,&nbsp;Stefano Ratti ,&nbsp;Lucia Manzoli ,&nbsp;Lucio Cocco ,&nbsp;Matilde Y. Follo","doi":"10.1016/j.jbior.2024.101014","DOIUrl":"10.1016/j.jbior.2024.101014","url":null,"abstract":"<div><p>Myelodysplastic Syndromes, a heterogeneous group of hematological disorders, are characterized by abnormalities in phosphoinositide-dependent signaling, epigenetic regulators, apoptosis, and cytokine interactions within the bone marrow microenvironment, contributing to disease pathogenesis and neoplastic growth. Comprehensive knowledge of these pathways is crucial for the development of innovative therapies that aim to restore normal apoptosis and improve patient outcomes.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"91 ","pages":"Article 101014"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212492624000022/pdfft?md5=14abee68b88a77ad36e9857499a566e7&pid=1-s2.0-S2212492624000022-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139502123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biological function, topology, and quantification of plasma membrane Ceramide 质膜神经酰胺的生物功能、拓扑结构和定量。
Advances in biological regulation Pub Date : 2023-12-14 DOI: 10.1016/j.jbior.2023.101009
Daniel Canals , Yusuf A. Hannun
{"title":"Biological function, topology, and quantification of plasma membrane Ceramide","authors":"Daniel Canals ,&nbsp;Yusuf A. Hannun","doi":"10.1016/j.jbior.2023.101009","DOIUrl":"10.1016/j.jbior.2023.101009","url":null,"abstract":"<div><p><span>Over the past 30 years, a growing body of evidence has revealed the regulatory role of the lipid </span>ceramide<span> in various cellular functions. The structural diversity of ceramide, resulting in numerous species, and its distinct distribution within subcellular compartments may account for its wide range of functions. However, our ability to study the potential role of ceramide in specific subcellular membranes has been limited. Several works have shown mitochondrial, Golgi, and plasma membrane ceramide to mediate signaling pathways<span> independently. These results have started to shift the focus on ceramide signaling research toward specific membrane pools. Nonetheless, the challenge arises from the substantial intracellular ceramide content, hindering efforts to quantify its presence in particular membranes. Recently, we have developed the first method capable of detecting and quantifying ceramide in the plasma membrane, leading to unexpected results such as detecting different pools of ceramide responding to drug concentration or time. This review summarizes the historical context that defined the idea of pools of ceramide, the studies on plasma membrane ceramide as a bioactive entity, and the tools available for its study, especially the new method to detect and, for the first time, quantify plasma membrane ceramide. We believe this method will open new avenues for researching sphingolipid signaling and metabolism.</span></span></p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"91 ","pages":"Article 101009"},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138827589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanistic insight on the role of iRhom2-TNF-α-BAFF signaling pathway in various autoimmune disorders iRhom2-TNF-α-BAFF 信号通路在各种自身免疫性疾病中的作用机制研究
Advances in biological regulation Pub Date : 2023-12-14 DOI: 10.1016/j.jbior.2023.101011
Shradha Devi Dwivedi , Rashi Shukla , Krishna Yadav , Lokendra Singh Rathor , Deependra Singh , Manju Rawat Singh
{"title":"Mechanistic insight on the role of iRhom2-TNF-α-BAFF signaling pathway in various autoimmune disorders","authors":"Shradha Devi Dwivedi ,&nbsp;Rashi Shukla ,&nbsp;Krishna Yadav ,&nbsp;Lokendra Singh Rathor ,&nbsp;Deependra Singh ,&nbsp;Manju Rawat Singh","doi":"10.1016/j.jbior.2023.101011","DOIUrl":"10.1016/j.jbior.2023.101011","url":null,"abstract":"<div><p><span><span><span>iRhom2 is a crucial cofactor involved in upregulation of TNF receptors<span> (TNFRs) and the pro-inflammatory cytokine tumor necrosis factor (TNF-) from the cell surface by </span></span>ADAM17. Tumor necrosis factor- α converting </span>enzyme<span><span> (TACE) is another name given to ADAM17. Many membrane attached biologically active molecules are cleaved by this enzyme which includes TNFRs<span><span> and the pro-inflammatory cytokine tumor necrosis factor- α. The TNF receptors are of two types TNFR1 and TNFR2. iRhom2 belongs to the pseudo-protease class of rhomboid family, its abundance is observed in the immune cells. </span>Biological activity of ADAM17 is affected in multiple levels by the iRhom2. ADAM17 is trafficked into the </span></span>Golgi apparatus by the action of iRhom2, where it gets matured proteolytically and is stimulated to perform its function on the cell surface. This process of activation of ADAM17 results in the protection of the organism from the cascade of inflammatory reactions, as this activation blocks the TNF- α mediated secretion responsible for inflammatory responses produced. Present paper illustrates about the iRhom2-TNF-α-BAFF </span></span>signaling pathway<span> and its correlation with several autoimmune disorders such as Rheumatoid Arthritis, Systemic Lupus Erythematosus, Hemophilia Arthropathy, Alzheimer's disease and Tylosis with esophageal cancer etc.</span></p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"92 ","pages":"Article 101011"},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139020958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IP8: A quantitatively minor inositol pyrophosphate signaling molecule that punches above its weight IP8:一个在数量上微不足道的焦磷酸肌醇信号分子,却有超乎寻常的作用
Advances in biological regulation Pub Date : 2023-12-01 DOI: 10.1016/j.jbior.2023.101002
Chunfang Gu , Xingyao Li , Guangning Zong , Huanchen Wang , Stephen B. Shears
{"title":"IP8: A quantitatively minor inositol pyrophosphate signaling molecule that punches above its weight","authors":"Chunfang Gu ,&nbsp;Xingyao Li ,&nbsp;Guangning Zong ,&nbsp;Huanchen Wang ,&nbsp;Stephen B. Shears","doi":"10.1016/j.jbior.2023.101002","DOIUrl":"https://doi.org/10.1016/j.jbior.2023.101002","url":null,"abstract":"<div><p><span>The inositol<span> pyrophosphates (PP-IPs) are specialized members of the wider inositol phosphate signaling family that possess functionally significant diphosphate groups. The PP-IPs exhibit remarkable functionally versatility throughout the eukaryotic kingdoms. However, a quantitatively minor PP-IP – 1,5 bisdiphosphoinositol tetrakisphosphate (1,5-IP</span></span><sub>8</sub><span>) – has received considerably less attention from the cell signalling community. The main purpose of this review is to summarize recently-published data which have now brought 1,5-IP</span><sub>8</sub><span> into the spotlight, by expanding insight into the molecular mechanisms by which this polyphosphate regulates many fundamental biological processes.</span></p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"91 ","pages":"Article 101002"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138557336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structural basis for the conserved roles of PI4KA and its regulatory partners and their misregulation in disease PI4KA及其调控伙伴的保守作用及其在疾病中的失调的结构基础
Advances in biological regulation Pub Date : 2023-11-10 DOI: 10.1016/j.jbior.2023.100996
Sushant Suresh , John E. Burke
{"title":"Structural basis for the conserved roles of PI4KA and its regulatory partners and their misregulation in disease","authors":"Sushant Suresh ,&nbsp;John E. Burke","doi":"10.1016/j.jbior.2023.100996","DOIUrl":"https://doi.org/10.1016/j.jbior.2023.100996","url":null,"abstract":"<div><p>The type III Phosphatidylinositol<span><span> 4-kinase alpha (PI4KA) is an essential lipid kinase that is a master regulator of </span>phosphoinositide<span><span> signalling at the plasma membrane (PM). It produces the predominant pool of phosphatidylinositol 4-phosphate (PI4P) at the PM, with this being essential in lipid transport and in regulating the PLC and PI3K </span>signalling pathways<span>. PI4KA is essential and is highly conserved in all eukaryotes. In yeast, the PI4KA ortholog stt4 predominantly exists as a heterodimer with its regulatory partner ypp1. In higher eukaryotes, PI4KA instead primarily forms a heterotrimer with a TTC7 subunit (ortholog of ypp1) and a FAM126 subunit. In all eukaryotes PI4KA is recruited to the plasma membrane by the protein EFR3, which does not directly bind PI4KA, but instead binds to the TTC7/ypp1 regulatory partner. Misregulation in PI4KA or its regulatory partners is involved in myriad human diseases, including loss of function mutations in neurodevelopmental and inflammatory intestinal disorders and gain of function in human cancers. This review describes an in-depth analysis of the structure function of PI4KA and its regulatory partners, with a major focus on comparing and contrasting the differences in regulation of PI4KA throughout evolution.</span></span></span></p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"90 ","pages":"Article 100996"},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134652434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Site-specific crosslinking reveals Phosphofructokinase-L inhibition drives self-assembly and attenuation of protein interactions 位点特异性交联揭示磷酸果糖激酶-L的抑制作用驱动蛋白质相互作用的自组装和减弱。
Advances in biological regulation Pub Date : 2023-09-27 DOI: 10.1016/j.jbior.2023.100987
Athira Sivadas , Eli Fritz McDonald , Sydney O. Shuster , Caitlin M. Davis , Lars Plate
{"title":"Site-specific crosslinking reveals Phosphofructokinase-L inhibition drives self-assembly and attenuation of protein interactions","authors":"Athira Sivadas ,&nbsp;Eli Fritz McDonald ,&nbsp;Sydney O. Shuster ,&nbsp;Caitlin M. Davis ,&nbsp;Lars Plate","doi":"10.1016/j.jbior.2023.100987","DOIUrl":"10.1016/j.jbior.2023.100987","url":null,"abstract":"<div><p>Phosphofructokinase is the central enzyme in glycolysis and constitutes a highly regulated step. The liver isoform (PFKL) compartmentalizes during activation and inhibition <em>in vitro</em> and <em>in vivo,</em> respectively. Compartmentalized PFKL is hypothesized to modulate metabolic flux consistent with its central role as the rate limiting step in glycolysis. PFKL tetramers self-assemble at two interfaces in the monomer (interface 1 and 2), yet how these interfaces contribute to PFKL compartmentalization and drive protein interactions remains unclear. Here, we used site-specific incorporation of noncanonical photocrosslinking amino acids to identify PFKL interactors at interface 1, 2, and the active site. Tandem mass tag-based quantitative interactomics reveals interface 2 as a hotspot for PFKL interactions, particularly with cytoskeletal, glycolytic, and carbohydrate derivative metabolic proteins. Furthermore, PFKL compartmentalization into puncta was observed in human cells using citrate inhibition. Puncta formation attenuated crosslinked protein-protein interactions with the cytoskeleton at interface 2. This result suggests that PFKL compartmentalization sequesters interface 2, but not interface 1, and may modulate associated protein assemblies with the cytoskeleton.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"90 ","pages":"Article 100987"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41113652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phosphorylation impacts GLE1 nuclear localization and association with DDX1 磷酸化影响GLE1核定位和与DDX1的结合。
Advances in biological regulation Pub Date : 2023-09-27 DOI: 10.1016/j.jbior.2023.100990
Manisha Sharma , Aaron C. Mason , T. Renee Dawson , Susan R. Wente
{"title":"Phosphorylation impacts GLE1 nuclear localization and association with DDX1","authors":"Manisha Sharma ,&nbsp;Aaron C. Mason ,&nbsp;T. Renee Dawson ,&nbsp;Susan R. Wente","doi":"10.1016/j.jbior.2023.100990","DOIUrl":"10.1016/j.jbior.2023.100990","url":null,"abstract":"<div><p>Gle1 regulates gene expression at multiple steps from transcription to mRNA export to translation under stressed and non-stressed conditions. To better understand Gle1 function in stressed human cells, specific antibodies were generated that recognized the phosphorylation of threonine residue 102 (T102) in Gle1. A series of <em>in vitro</em> kinase assays indicated that T102 phosphorylation serves as a priming event for further phosphorylation in Gle1's N-terminal low complexity cluster. Indirect immunofluorescence microscopy with the anti-Gle1-pT102 antibodies revealed that basally phosphorylated Gle1 was pre-dominantly nuclear with punctate distribution; however, under sodium arsenite-induced stress, more cytoplasmic localization was detected. Immunoprecipitation with the anti-Gle1-pT102 antibody resulted in co-isolation of Gle1-pT102 with the DEAD-box protein DDX1 in a phosphatase sensitive manner. This suggested Gle1 phosphorylation might be linked to its role in regulating DDX1 during transcription termination. Notably, whereas the total Gle1-DDX1 association was decreased when Gle1 nucleocytoplasmic shuttling was disrupted, co-isolation of Gle1-pT102 and DDX1 increased under the same conditions. Taken together, these studies demonstrated that Gle1 phosphorylation impacts its cellular distribution and potentially drives nuclear Gle1 functions in transcription termination. We propose a model wherein phosphorylation of Gle1 either reduces its nucleocytoplasmic shuttling capacity or increases its binding affinity with nuclear interaction partners.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"90 ","pages":"Article 100990"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41106548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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