Nature Reviews Molecular Cell Biology最新文献_第9页

Targeted protein degradation: from mechanisms to clinic 靶向蛋白质降解：从机制到临床

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-04-29 DOI: 10.1038/s41580-024-00729-9

Jonathan M. Tsai, Radosław P. Nowak, Benjamin L. Ebert, Eric S. Fischer

{"title":"Targeted protein degradation: from mechanisms to clinic","authors":"Jonathan M. Tsai, Radosław P. Nowak, Benjamin L. Ebert, Eric S. Fischer","doi":"10.1038/s41580-024-00729-9","DOIUrl":"10.1038/s41580-024-00729-9","url":null,"abstract":"Targeted protein degradation refers to the use of small molecules to induce the selective degradation of proteins. In its most common form, this degradation is achieved through ligand-mediated neo-interactions between ubiquitin E3 ligases — the principal waste disposal machines of a cell — and the protein targets of interest, resulting in ubiquitylation and subsequent proteasomal degradation. Notable advances have been made in biological and mechanistic understanding of serendipitously discovered degraders. This improved understanding and novel chemistry has not only provided clinical proof of concept for targeted protein degradation but has also led to rapid growth of the field, with dozens of investigational drugs in active clinical trials. Two distinct classes of protein degradation therapeutics are being widely explored: bifunctional PROTACs and molecular glue degraders, both of which have their unique advantages and challenges. Here, we review the current landscape of targeted protein degradation approaches and how they have parallels in biological processes. We also outline the ongoing clinical exploration of novel degraders and provide some perspectives on the directions the field might take. This article reviews the current landscape of targeted protein degradation approaches and how they have parallels in biological processes. The authors also outline the ongoing clinical exploration of novel degraders and provide some perspectives on the directions the field might take.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 9","pages":"740-757"},"PeriodicalIF":81.3,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140808341","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

Epithelial–mesenchymal transition in tissue repair and degeneration 组织修复和退化过程中的上皮-间质转化

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-04-29 DOI: 10.1038/s41580-024-00733-z

Khalil Kass Youssef, M. Angela Nieto

{"title":"Epithelial–mesenchymal transition in tissue repair and degeneration","authors":"Khalil Kass Youssef, M. Angela Nieto","doi":"10.1038/s41580-024-00733-z","DOIUrl":"10.1038/s41580-024-00733-z","url":null,"abstract":"Epithelial–mesenchymal transitions (EMTs) are the epitome of cell plasticity in embryonic development and cancer; during EMT, epithelial cells undergo dramatic phenotypic changes and become able to migrate to form different tissues or give rise to metastases, respectively. The importance of EMTs in other contexts, such as tissue repair and fibrosis in the adult, has become increasingly recognized and studied. In this Review, we discuss the function of EMT in the adult after tissue damage and compare features of embryonic and adult EMT. Whereas sustained EMT leads to adult tissue degeneration, fibrosis and organ failure, its transient activation, which confers phenotypic and functional plasticity on somatic cells, promotes tissue repair after damage. Understanding the mechanisms and temporal regulation of different EMTs provides insight into how some tissues heal and has the potential to open new therapeutic avenues to promote repair or regeneration of tissue damage that is currently irreversible. We also discuss therapeutic strategies that modulate EMT that hold clinical promise in ameliorating fibrosis, and how precise EMT activation could be harnessed to enhance tissue repair. During embryonic epithelial–mesenchymal transition, epithelial cells undergo substantial phenotypic changes and acquire migration capacity. This Review compares embryonic and adult non-cancer EMTs and discusses the role of EMTs in adult tissue repair and fibrosis, highlighting therapeutic opportunities to modulate EMT to reduce fibrosis and promote repair.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 9","pages":"720-739"},"PeriodicalIF":81.3,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814790","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

The senescence-associated secretory phenotype and its physiological and pathological implications 衰老相关的分泌表型及其生理和病理影响

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-04-23 DOI: 10.1038/s41580-024-00727-x

Boshi Wang, Jin Han, Jennifer H. Elisseeff, Marco Demaria

{"title":"The senescence-associated secretory phenotype and its physiological and pathological implications","authors":"Boshi Wang, Jin Han, Jennifer H. Elisseeff, Marco Demaria","doi":"10.1038/s41580-024-00727-x","DOIUrl":"10.1038/s41580-024-00727-x","url":null,"abstract":"Cellular senescence is a state of terminal growth arrest associated with the upregulation of different cell cycle inhibitors, mainly p16 and p21, structural and metabolic alterations, chronic DNA damage responses, and a hypersecretory state known as the senescence-associated secretory phenotype (SASP). The SASP is the major mediator of the paracrine effects of senescent cells in their tissue microenvironment and of various local and systemic biological functions. In this Review, we discuss the composition, dynamics and heterogeneity of the SASP as well as the mechanisms underlying its induction and regulation. We describe the various biological properties of the SASP, its beneficial and detrimental effects in different physiological and pathological settings, and its impact on overall health span. Finally, we discuss the use of the SASP as a biomarker and of SASP inhibitors as senomorphic interventions to treat cancer and other age-related conditions. The senescence-associated secretory phenotype (SASP) mediates the tissue effects of senescent cells. This Review discusses the composition, regulation and various biological implications of the SASP and its uses as a biomarker and a target of senomorphic drugs to treat cancer and other age-related conditions.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 12","pages":"958-978"},"PeriodicalIF":81.3,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140637626","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

Is endocytosis by caveolae dependent on dynamin? 洞穴小体的内吞作用依赖于达纳明吗？

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-04-22 DOI: 10.1038/s41580-024-00735-x

Robert G. Parton, Justin W. Taraska, Richard Lundmark

引用次数: 0

Relaying gasdermin D to the membrane 将气敏素 D 转运到膜上

IF 112.7 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-04-17 DOI: 10.1038/s41580-024-00737-9

Lisa Heinke

引用次数: 0

Early insights into co-translational assembly of protein complexes 对蛋白质复合物共翻译组装的初步认识

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-04-12 DOI: 10.1038/s41580-024-00728-w

Ayala Shiber

引用次数: 0

In memoriam Judy Campisi: spreading cellular senescence 悼念朱迪-坎皮西：传播细胞衰老

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-04-12 DOI: 10.1038/s41580-024-00736-w

Fabrizio d’Adda di Fagagna

引用次数: 0

Mechanical state transitions in the regulation of tissue form and function 调节组织形态和功能的机械状态转换

IF 81.3 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-04-10 DOI: 10.1038/s41580-024-00719-x

Yanlan Mao, Sara A. Wickström

{"title":"Mechanical state transitions in the regulation of tissue form and function","authors":"Yanlan Mao, Sara A. Wickström","doi":"10.1038/s41580-024-00719-x","DOIUrl":"10.1038/s41580-024-00719-x","url":null,"abstract":"From embryonic development, postnatal growth and adult homeostasis to reparative and disease states, cells and tissues undergo constant changes in genome activity, cell fate, proliferation, movement, metabolism and growth. Importantly, these biological state transitions are coupled to changes in the mechanical and material properties of cells and tissues, termed mechanical state transitions. These mechanical states share features with physical states of matter, liquids and solids. Tissues can switch between mechanical states by changing behavioural dynamics or connectivity between cells. Conversely, these changes in tissue mechanical properties are known to control cell and tissue function, most importantly the ability of cells to move or tissues to deform. Thus, tissue mechanical state transitions are implicated in transmitting information across biological length and time scales, especially during processes of early development, wound healing and diseases such as cancer. This Review will focus on the biological basis of tissue-scale mechanical state transitions, how they emerge from molecular and cellular interactions, and their roles in organismal development, homeostasis, regeneration and disease. Tissues undergo changes in their mechanical and material properties through alterations in cytoskeleton organization, extracellular matrix adhesion and cell–cell connectivity. These mechanical state transitions orchestrate cell proliferation and movement and tissue growth during development, in adult tissue repair and in disease contexts.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 8","pages":"654-670"},"PeriodicalIF":81.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140545123","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

Modelling tauopathies 牛磺酸病建模

IF 112.7 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-04-09 DOI: 10.1038/s41580-024-00734-y

Kim Baumann

引用次数: 0

A novel photosystem assembly line worker 新型光系统装配线工人

IF 112.7 1区生物学

Nature Reviews Molecular Cell Biology Pub Date : 2024-04-08 DOI: 10.1038/s41580-024-00732-0

Lisa Heinke

引用次数: 0