Nature Reviews Molecular Cell Biology最新文献_第6页

Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases 染色质和基因组不稳定性在细胞衰老中的作用及其与衰老和相关疾病的关系

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-10-03 DOI: 10.1038/s41580-024-00775-3

Zeming Wu, Jing Qu, Guang-Hui Liu

{"title":"Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases","authors":"Zeming Wu, Jing Qu, Guang-Hui Liu","doi":"10.1038/s41580-024-00775-3","DOIUrl":"10.1038/s41580-024-00775-3","url":null,"abstract":"Ageing is a complex biological process in which a gradual decline in physiological fitness increases susceptibility to diseases such as neurodegenerative disorders and cancer. Cellular senescence, a state of irreversible cell-growth arrest accompanied by functional deterioration, has emerged as a pivotal driver of ageing. In this Review, we discuss how heterochromatin loss, telomere attrition and DNA damage contribute to cellular senescence, ageing and age-related diseases by eliciting genome instability, innate immunity and inflammation. We also discuss how emerging therapeutic strategies could restore heterochromatin stability, maintain telomere integrity and boost the DNA repair capacity, and thus counteract cellular senescence and ageing-associated pathologies. Finally, we outline current research challenges and future directions aimed at better comprehending and delaying ageing. Heterochromatin loss, telomere attrition and DNA damage induce cellular senescence by eliciting genome instability and innate immunity responses, thereby promoting ageing and age-related diseases. This Review discusses the underlying mechanisms of these processes and emerging cell-senescence therapeutics that target them.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 12","pages":"979-1000"},"PeriodicalIF":81.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Mechanisms and regulation of substrate degradation by the 26S proteasome 26S 蛋白酶体降解底物的机制和调控

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-10-03 DOI: 10.1038/s41580-024-00778-0

Connor Arkinson, Ken C. Dong, Christine L. Gee, Andreas Martin

{"title":"Mechanisms and regulation of substrate degradation by the 26S proteasome","authors":"Connor Arkinson, Ken C. Dong, Christine L. Gee, Andreas Martin","doi":"10.1038/s41580-024-00778-0","DOIUrl":"10.1038/s41580-024-00778-0","url":null,"abstract":"The 26S proteasome is involved in degrading and regulating the majority of proteins in eukaryotic cells, which requires a sophisticated balance of specificity and promiscuity. In this Review, we discuss the principles that underly substrate recognition and ATP-dependent degradation by the proteasome. We focus on recent insights into the mechanisms of conventional ubiquitin-dependent and ubiquitin-independent protein turnover, and discuss the plethora of modulators for proteasome function, including substrate-delivering cofactors, ubiquitin ligases and deubiquitinases that enable the targeting of a highly diverse substrate pool. Furthermore, we summarize recent progress in our understanding of substrate processing upstream of the 26S proteasome by the p97 protein unfoldase. The advances in our knowledge of proteasome structure, function and regulation also inform new strategies for specific inhibition or harnessing the degradation capabilities of the proteasome for the treatment of human diseases, for instance, by using proteolysis targeting chimera molecules or molecular glues. Most proteins are degraded and regulated by the 26S proteasome. A balance of specificity and promiscuity underlies substrate recognition and ATP-dependent degradation, which can occur in a ubiquitin-dependent or ubiquitin-independent manner. Recent insights into the mechanisms and regulation of substrate delivery, processing and degradation will inform new strategies for the treatment of human diseases.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 2","pages":"104-122"},"PeriodicalIF":81.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Rise and SINE: roles of transcription factors and retrotransposons in zygotic genome activation 崛起与SINE：转录因子和逆转录转座子在子代基因组激活中的作用

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-10-02 DOI: 10.1038/s41580-024-00772-6

Pavel Kravchenko, Kikuë Tachibana

{"title":"Rise and SINE: roles of transcription factors and retrotransposons in zygotic genome activation","authors":"Pavel Kravchenko, Kikuë Tachibana","doi":"10.1038/s41580-024-00772-6","DOIUrl":"10.1038/s41580-024-00772-6","url":null,"abstract":"In sexually reproducing organisms, life begins with the fusion of transcriptionally silent gametes, the oocyte and sperm. Although initiation of transcription in the embryo, known as zygotic genome activation (ZGA), is universally required for development, the transcription factors regulating this process are poorly conserved. In this Perspective, we discuss recent insights into the mechanisms of ZGA in totipotent mammalian embryos, namely ZGA regulation by several transcription factors, including by orphan nuclear receptors (OrphNRs) such as the pioneer transcription factor NR5A2, and by factors of the DUX, TPRX and OBOX families. We performed a meta-analysis and compiled a list of pan-ZGA genes, and found that most of these genes are indeed targets of the above transcription factors. Remarkably, more than a third of these ZGA genes appear to be regulated both by OrphNRs such as NR5A2 and by OBOX proteins, whose motifs co-occur in SINE B1 retrotransposable elements, which are enriched near ZGA genes. We propose that ZGA in mice is activated by recruitment of multiple transcription factors to SINE B1 elements that function as enhancers, and discuss a potential relevance of this mechanism to Alu retrotransposable elements in human ZGA. Although zygotic genome activation (ZGA) is universally required for development, the responsible transcription factors are poorly conserved. In mammalian totipotent embryos, (pioneer) transcription factors of two families co-regulate many ZGA genes by binding to nearby SINE retrotransposons, which thus function as their enhancers.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 1","pages":"68-79"},"PeriodicalIF":81.3,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Proteoforms: a tale of two (initiation) sites 蛋白质形式：两个（启动）位点的故事

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-10-01 DOI: 10.1038/s41580-024-00788-y

Eytan Zlotorynski

引用次数: 0

The role and regulation of integrins in cell migration and invasion 整合素在细胞迁移和侵袭中的作用与调控

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-09-30 DOI: 10.1038/s41580-024-00777-1

Megan R. Chastney, Jasmin Kaivola, Veli-Matti Leppänen, Johanna Ivaska

{"title":"The role and regulation of integrins in cell migration and invasion","authors":"Megan R. Chastney, Jasmin Kaivola, Veli-Matti Leppänen, Johanna Ivaska","doi":"10.1038/s41580-024-00777-1","DOIUrl":"10.1038/s41580-024-00777-1","url":null,"abstract":"Integrin receptors are the main molecular link between cells and the extracellular matrix (ECM) as well as mediating cell–cell interactions. Integrin–ECM binding triggers the formation of heterogeneous multi-protein assemblies termed integrin adhesion complexes (IACs) that enable integrins to transform extracellular cues into intracellular signals that affect many cellular processes, especially cell motility. Cell migration is essential for diverse physiological and pathological processes and is dysregulated in cancer to favour cell invasion and metastasis. Here, we discuss recent findings on the role of integrins in cell migration with a focus on cancer cell dissemination. We review how integrins regulate the spatial distribution and dynamics of different IACs, covering classical focal adhesions, emerging adhesion types and adhesion regulation. We discuss the diverse roles integrins have during cancer progression from cell migration across varied ECM landscapes to breaching barriers such as the basement membrane, and eventual colonization of distant organs. Integrin receptors connect cells to the extracellular matrix, mediating cell interactions, adhesion and signalling. This Review discusses integrin function in cell migration, including integrin activation, integrin-based adhesion types and their roles in cancer cell dissemination.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 2","pages":"147-167"},"PeriodicalIF":81.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Author Correction: The role of the haematopoietic stem cell niche in development and ageing 作者更正：造血干细胞龛在发育和衰老中的作用

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-09-26 DOI: 10.1038/s41580-024-00787-z

Terri L. Cain, Marta Derecka, Shannon McKinney-Freeman

引用次数: 0

Author Correction: Structural biology and molecular pharmacology of voltage-gated ion channels 作者更正：电压门控离子通道的结构生物学和分子药理学

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-09-24 DOI: 10.1038/s41580-024-00786-0

Jian Huang, Xiaojing Pan, Nieng Yan

引用次数: 0

Publisher Correction: Generation of nanoscopic membrane curvature for membrane trafficking 出版商更正：生成纳米级膜曲率，促进膜贩运。

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-09-23 DOI: 10.1038/s41580-024-00782-4

Michael M. Kozlov, Justin W. Taraska

引用次数: 0

The role of the haematopoietic stem cell niche in development and ageing 造血干细胞龛在发育和衰老中的作用

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-09-10 DOI: 10.1038/s41580-024-00770-8

Terri L. Cain, Marta Derecka, Shannon McKinney-Freeman

{"title":"The role of the haematopoietic stem cell niche in development and ageing","authors":"Terri L. Cain, Marta Derecka, Shannon McKinney-Freeman","doi":"10.1038/s41580-024-00770-8","DOIUrl":"10.1038/s41580-024-00770-8","url":null,"abstract":"Blood production depends on rare haematopoietic stem cells (HSCs) and haematopoietic stem and progenitor cells (HSPCs) that ultimately take up residence in the bone marrow during development. HSPCs and HSCs are subject to extrinsic regulation by the bone marrow microenvironment, or niche. Studying the interactions between HSCs and their niche is critical for improving ex vivo culturing conditions and genetic manipulation of HSCs, which is pivotal for improving autologous HSC therapies and transplantations. Additionally, understanding how the complex molecular network in the bone marrow is altered during ageing is paramount for developing novel therapeutics for ageing-related haematopoietic disorders. HSCs are unique amongst stem and progenitor cell pools in that they engage with multiple physically distinct niches during their ontogeny. HSCs are specified from haemogenic endothelium in the aorta, migrate to the fetal liver and, ultimately, colonize their final niche in the bone marrow. Recent studies employing single-cell transcriptomics and microscopy have identified novel cellular interactions that govern HSC specification and engagement with their niches throughout ontogeny. New lineage-tracing models and microscopy tools have raised questions about the numbers of HSCs specified, as well as the functional consequences of HSCs interacting with each developmental niche. Advances have also been made in understanding how these niches are modified and perturbed during ageing, and the role of these altered interactions in haematopoietic diseases. In this Review, we discuss these new findings and highlight the questions that remain to be explored. Blood production depends on haematopoietic stem cells (HSCs) and progenitor cells, which are regulated by their microenvironment or niche. New lineage-tracing models and microscopy tools are increasing the understanding of HSC specification and function, and how stem cell–niche interactions are perturbed during ageing.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 1","pages":"32-50"},"PeriodicalIF":81.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Mechanisms of mechanotransduction and physiological roles of PIEZO channels PIEZO 通道的机械传导机制和生理作用

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-09-09 DOI: 10.1038/s41580-024-00773-5

Bailong Xiao

{"title":"Mechanisms of mechanotransduction and physiological roles of PIEZO channels","authors":"Bailong Xiao","doi":"10.1038/s41580-024-00773-5","DOIUrl":"10.1038/s41580-024-00773-5","url":null,"abstract":"Mechanical force is an essential physical element that contributes to the formation and function of life. The discovery of the evolutionarily conserved PIEZO family, including PIEZO1 and PIEZO2 in mammals, as bona fide mechanically activated cation channels has transformed our understanding of how mechanical forces are sensed and transduced into biological activities. In this Review, I discuss recent structure–function studies that have illustrated how PIEZO1 and PIEZO2 adopt their unique structural design and curvature-based gating dynamics, enabling their function as dedicated mechanotransduction channels with high mechanosensitivity and selective cation conductivity. I also discuss our current understanding of the physiological and pathophysiological roles mediated by PIEZO channels, including PIEZO1-dependent regulation of development and functional homeostasis and PIEZO2-dominated mechanosensation of touch, tactile pain, proprioception and interoception of mechanical states of internal organs. Despite the remarkable progress in PIEZO research, this Review also highlights outstanding questions in the field. The mechanically activated cation channels PIEZO1 and PIEZO2 are crucial for mechanotransduction processes in mammals. This Review discusses the structural design and gating dynamics of PIEZO channels that enable their high mechanosensitivity, and highlights their physiological and pathological relevance.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 11","pages":"886-903"},"PeriodicalIF":81.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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