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Exploring the interaction dynamics of eukaryotic translation initiation factor 2. 真核生物翻译起始因子2相互作用动力学研究。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-06-30 DOI: 10.1042/BST20253022
Assen Marintchev
{"title":"Exploring the interaction dynamics of eukaryotic translation initiation factor 2.","authors":"Assen Marintchev","doi":"10.1042/BST20253022","DOIUrl":"10.1042/BST20253022","url":null,"abstract":"<p><p>Eukaryotic translation initiation typically involves recruitment of the 43S ribosomal pre-initiation complex (PIC) to the 5'-end of the mRNA to form the 48S PIC, followed by scanning in search of a start codon in a favorable nucleotide complex. The start codon is recognized through base-pairing with the anticodon of the initiator Met-tRNAi. The stringency of start codon selection controls the probability of initiation from a start codon in a suboptimal nucleotide context. Met-tRNAi itself is recruited to the 43S PIC by the eukaryotic translation initiation factor 2 (eIF2), in the form of the eIF2-GTP•Met-tRNAi ternary complex (TC). GTP hydrolysis by eIF2, promoted by its GTPase-activating protein eIF5, leads to the release of eIF2-GDP from the PIC. Recycling of eIF2-GDP to TC is promoted by the guanine nucleotide exchange factor eIF2B. Its inhibition by a number of stress factors triggers the integrated stress response (ISR). This review describes the recent advances in elucidating the interactions of eIF2 and its partners, with an emphasis on the timing and dynamics of their binding to, and release from the PIC. Special attention is given to the regulation of the stringency of start codon selection and the ISR. The discussion is mostly limited to translation initiation in mammals and budding yeast.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"593-602"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CRAC channels and patho-physiology of peripheral organ systems. CRAC通道与外周器官系统的病理生理。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-06-30 DOI: 10.1042/BST20253062
Rajesh Bhardwaj, Anant B Parekh
{"title":"CRAC channels and patho-physiology of peripheral organ systems.","authors":"Rajesh Bhardwaj, Anant B Parekh","doi":"10.1042/BST20253062","DOIUrl":"10.1042/BST20253062","url":null,"abstract":"<p><p>A rise in cytosolic Ca2+ is used as a key signalling messenger in eukaryotic cells. The Ca2+ signal drives life and death and controls myriad responses in between. Inherent in the use of such a multifarious signal is the danger of disease, arising from dysregulated Ca2+ signalling. One ancient, highly conserved and widespread Ca2+ entry pathway is the store-operated Ca2+ release-activated Ca2+ (CRAC) channel. Mutations in STIM1 and ORAI1, the genes that encode the functional channel, are tightly linked to a CRAC channelopathy in humans, which encompasses severe combined immune deficiency, myopathy and anhidrotic ectodermal dysplasia. Moreover, sustained Ca2+ entry through the channels leads to a range of systemic disorders, including acute pancreatitis, asthma and inflammatory bowel disease. In this review, we describe how aberrant CRAC channel activity causes a range of diseases, highlighting commonalities between these diverse pathologies.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"627-642"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
How do different cell populations orchestrate myelin regeneration? 不同的细胞群如何协调髓磷脂再生？
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-06-30 DOI: 10.1042/BST20231085
Sara Grassi, Alessandro Prinetti
{"title":"How do different cell populations orchestrate myelin regeneration?","authors":"Sara Grassi, Alessandro Prinetti","doi":"10.1042/BST20231085","DOIUrl":"10.1042/BST20231085","url":null,"abstract":"<p><p>Approximately 35 in 100,000 people are affected by diseases associated with loss of myelin, generally described as demyelinating diseases. Demyelinating diseases encompass many different pathological conditions characterized by heterogeneous and sometimes disease-specific etiopathological mechanisms. While several approaches aimed at ameliorating the symptoms and the progression of some of these diseases exist, the most effective cure for all demyelinating diseases would be regeneration of lost myelin. Myelin regeneration occurs spontaneously in the central nervous system in response to myelin damage but is inefficient for a variety of reasons, especially in human patients. In this review, we will discuss the contributions of different cell populations to the creation of conditions permissive for effective remyelination and to the formation of new myelin after injury. Moreover, we would like to highlight the importance of sphingolipids in the network of interactions between these cell populations. Mutations in genes encoding sphingolipid metabolic enzymes (such as GALC) represent a major risk factor for multiple sclerosis, and alterations in sphingolipid metabolism in specific cell types contribute to myelin damage. On the other hand, sphingolipid signaling, in particular through sphingosine 1 phosphate, directly affects the process of myelin regeneration, with distinct effects on different cellular populations.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"653-669"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Connecting tubules: mechanisms of endoplasmic reticulum membrane fusion. 连接小管：内质网膜融合机制。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-06-30 DOI: 10.1042/BST20253043
Eunhong Jang, Youngsoo Jun
{"title":"Connecting tubules: mechanisms of endoplasmic reticulum membrane fusion.","authors":"Eunhong Jang, Youngsoo Jun","doi":"10.1042/BST20253043","DOIUrl":"https://doi.org/10.1042/BST20253043","url":null,"abstract":"<p><p>Atlastins (ATLs) are integral dynamin-like GTPases that are critical for the formation and maintenance of the endoplasmic reticulum (ER) network, one of the most complex and essential organelles in eukaryotic cells. The ER, which is composed of interconnected tubules and sheets, serves vital functions, including calcium storage, protein and lipid synthesis, and inter-organelle communication. Homotypic membrane fusion, mediated by ATLs, ensures the tubular structure of the ER by generating and stabilizing three-way junctions. Humans express three ATL paralogs, called ATL1, ATL2, and ATL3, which have distinct expression patterns and regulatory mechanisms. Mutations in these proteins are linked to hereditary sensory neuropathies and hereditary spastic paraplegia, highlighting their critical importance in cellular and neuronal health. Here, we review recent studies providing insights into how ATLs are regulated by their N- and C-terminal extensions, as well as how extrinsic factors potentially regulate the activities of ATLs to establish and maintain the normal ER structure.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 3","pages":"699-707"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regulation of adipogenesis by nucleotides. 核苷酸对脂肪形成的调控。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-06-30 DOI: 10.1042/BST20253045
Julia A Pinette, Heather G Bryant, Jacob W Myers, Elma Zaganjor
{"title":"Regulation of adipogenesis by nucleotides.","authors":"Julia A Pinette, Heather G Bryant, Jacob W Myers, Elma Zaganjor","doi":"10.1042/BST20253045","DOIUrl":"https://doi.org/10.1042/BST20253045","url":null,"abstract":"<p><p>The process by which multipotent cells commit to differentiate into distinct cell types, eventually forming functional tissues and organisms, has fascinated scientists for decades. Consequently, numerous studies have contributed to our understanding of how transcription factors and signaling molecules regulate differentiation. A growing area of interest in the field centers around the role of nutrients and metabolic pathways in cell fate determination. This review focuses on adipogenesis (also termed hyperplasia), the formation of adipocytes, which are key sensors of nutrient availability. We will examine recent findings that reshape our understanding of how nucleotide metabolism regulates adipogenesis.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 3","pages":"687-697"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Extracellular membrane particles en route to the nucleus - exploring the VOR complex. 胞外膜颗粒在通往细胞核的途中-探索VOR复合体。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-06-30 DOI: 10.1042/BST20253005
Aurelio Lorico, Mark F Santos, Jana Karbanová, Denis Corbeil
{"title":"Extracellular membrane particles en route to the nucleus - exploring the VOR complex.","authors":"Aurelio Lorico, Mark F Santos, Jana Karbanová, Denis Corbeil","doi":"10.1042/BST20253005","DOIUrl":"10.1042/BST20253005","url":null,"abstract":"<p><p>Intercellular communication is an essential hallmark of multicellular organisms for their development and adult tissue homeostasis. Over the past two decades, attention has been focused on communication mechanisms based on various membrane structures, as illustrated by the burst of scientific literature in the field of extracellular vesicles (EVs). These lipid bilayer-bound nano- or microparticles, as vehicle-like devices, act as regulators in various biological and physiological processes. When EVs are internalized by recipient cells, their membrane and cytoplasmic cargoes can interfere with cellular activities, affecting pathways that regulate cell proliferation, differentiation, and migration. In cancer, EVs can transfer oncogenic factors, stimulate neo-angiogenesis and immunosuppression, reprogram stromal cells, and confer drug resistance traits, thereby remodeling the surrounding microenvironment. Although the mechanisms underlying EV biogenesis and uptake are now better understood, little is known about the spatiotemporal mechanism(s) of their actions after internalization. In this respect, we have shown that a fraction of endocytosed EVs reaches the nuclear compartment via the VOR (VAP-A-ORP3-Rab7) complex-mediated docking of late endosomes to the outer nuclear membrane in the nucleoplasmic reticulum, positioning and facilitating the transfer of EV cargoes into the nucleoplasm via nuclear pores. Here, we highlight the EV heterogeneity, the cellular pathways governing EV release and uptake by donor and recipient cells, respectively, and focus on a novel intracellular pathway leading to the nuclear transfer of EV cargoes. We will discuss how to intercept it, which could open up new avenues for clinical applications in which EVs and other small extracellular particles (e.g., retroviruses) are implicated.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"529-546"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in understanding the mechanisms of the human papillomavirus oncoproteins. 人乳头瘤病毒癌蛋白机制的研究进展。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-06-30 DOI: 10.1042/BST20253041
Denise Ijeoma Obanya, Louisa M Wootton, Ethan L Morgan
{"title":"Advances in understanding the mechanisms of the human papillomavirus oncoproteins.","authors":"Denise Ijeoma Obanya, Louisa M Wootton, Ethan L Morgan","doi":"10.1042/BST20253041","DOIUrl":"10.1042/BST20253041","url":null,"abstract":"<p><p>High-risk human papillomaviruses (HPVs) are responsible for almost all cervical cancer cases and a growing number of oropharyngeal and anogenital cancers. The primary HPV oncoproteins, E6 and E7, act together to manipulate multiple cellular pathways that can ultimately result in malignant transformation. This includes the deregulation of several signalling pathways that regulate cell proliferation, cell cycle progression and cell survival. Although multiple functions of HPV E6 and E7 in driving oncogenesis are well known, recent studies have uncovered novel oncogenic functions of the HPV oncoproteins, including the manipulation of emerging mechanisms of cancer development, such as epigenetic modifications, cellular plasticity and genomic instability. This review explores current advances in understanding how the HPV oncoproteins interact with these cellular processes, highlighting potential therapeutic targets in HPV-associated cancers.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"565-577"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cdk activation by phosphorylation: linking growth signals to cell cycle control. 磷酸化激活Cdk：将生长信号与细胞周期控制联系起来。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-05-09 DOI: 10.1042/BST20253004
Heidi M Blank, Eun-Gyu No, Michael Polymenis
{"title":"Cdk activation by phosphorylation: linking growth signals to cell cycle control.","authors":"Heidi M Blank, Eun-Gyu No, Michael Polymenis","doi":"10.1042/BST20253004","DOIUrl":"10.1042/BST20253004","url":null,"abstract":"<p><p>Cells adjust their proliferation in response to extrinsic factors and nutrients. Such inputs must reach the cell cycle machinery to ensure proper cell proliferation. This minireview focuses on evidence suggesting that phosphorylating the T-loop domain of cyclin-dependent kinases may be a critical and conserved conduit for these external signals. Understanding this regulatory mechanism could provide crucial insights into how all eukaryotic cells integrate external information to decide whether or not to divide.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 2","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recent advances in understanding the role of extracellular vesicles from probiotics in intestinal immunity signaling. 益生菌胞外囊泡在肠道免疫信号传导中的作用研究进展。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-04-30 DOI: 10.1042/BST20240150
Atsushi Kurata, Koichi Uegaki
{"title":"Recent advances in understanding the role of extracellular vesicles from probiotics in intestinal immunity signaling.","authors":"Atsushi Kurata, Koichi Uegaki","doi":"10.1042/BST20240150","DOIUrl":"10.1042/BST20240150","url":null,"abstract":"<p><p>The diverse functions of gut symbiotic bacteria are attracting attention for their potential as probiotics. Some of those bacteria release extracellular vesicles (EVs), spherical structures of approximately 20-400 nm in diameter, outside their cell bodies. Recent research has significantly advanced our understanding of the physicochemical and biochemical properties, functions, and host-cell interactions of EVs released by probiotic bacteria used in food fermentation, such as lactic acid bacteria, bifidobacteria, butyric acid bacteria, and acetic acid bacteria. However, concerns have been raised regarding the use of these EVs as postbiotics. In this review, we discuss the newly discovered roles of EVs in the gut immune signaling and the challenges associated with their application as postbiotics.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 2","pages":"419-429"},"PeriodicalIF":3.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single-molecule study of the dynamics of the molecular chaperone Hsp70 during the functional cycle. 分子伴侣蛋白Hsp70在功能周期中的单分子动力学研究。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-04-30 DOI: 10.1042/BST20230831
Huimin Hu, Ming Yang, Sarah Perrett, Si Wu
{"title":"Single-molecule study of the dynamics of the molecular chaperone Hsp70 during the functional cycle.","authors":"Huimin Hu, Ming Yang, Sarah Perrett, Si Wu","doi":"10.1042/BST20230831","DOIUrl":"10.1042/BST20230831","url":null,"abstract":"<p><p>The 70-kDa heat shock protein, Hsp70, is a key chaperone involved in cellular protein homeostasis. The structure of the Hsp70 protein family is highly conserved, including a nucleotide-binding domain (NBD) and a substrate-binding domain (SBD). ATP binding and hydrolysis in the NBD of Hsp70 regulates the binding and release of substrates in the SBD via interdomain allosteric communication. Growing evidence shows that the conformational dynamics of Hsp70 are crucial for its function, which are difficult to probe by traditional bulk-based methods. Single-molecule techniques are emerging as powerful tools to explore the dynamics of proteins that are obscured in bulk measurements. In this review, we summarize recent progress in the study of the molecular dynamics of Hsp70 and its interactions with cochaperones and substrates using single-molecule fluorescence spectroscopy and single-molecule force spectroscopy. We discuss how the application of single-molecule techniques facilitates a deeper understanding of the mechanistic details of the chaperone functions of Hsp70.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 2","pages":"461-471"},"PeriodicalIF":3.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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