Biochemical Society transactions最新文献_第9页

Using human disease mutations to understand de novo DNA methyltransferase function. 利用人类疾病突变了解 DNA 甲基转移酶的功能。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-10-30 DOI: 10.1042/BST20231017

Willow Rolls, Marcus D Wilson, Duncan Sproul

{"title":"Using human disease mutations to understand de novo DNA methyltransferase function.","authors":"Willow Rolls, Marcus D Wilson, Duncan Sproul","doi":"10.1042/BST20231017","DOIUrl":"10.1042/BST20231017","url":null,"abstract":"DNA methylation is a repressive epigenetic mark that is pervasive in mammalian genomes. It is deposited by DNA methyltransferase enzymes (DNMTs) that are canonically classified as having de novo (DNMT3A and DNMT3B) or maintenance (DNMT1) function. Mutations in DNMT3A and DNMT3B cause rare Mendelian diseases in humans and are cancer drivers. Mammalian DNMT3 methyltransferase activity is regulated by the non-catalytic region of the proteins which contain multiple chromatin reading domains responsible for DNMT3A and DNMT3B recruitment to the genome. Characterising disease-causing missense mutations has been central in dissecting the function and regulation of DNMT3A and DNMT3B. These observations have also motivated biochemical studies that provide the molecular details as to how human DNMT3A and DNMT3B mutations drive disorders. Here, we review progress in this area highlighting recent work that has begun dissecting the function of the disordered N-terminal regions of DNMT3A and DNMT3B. These studies have elucidated that the N-terminal regions of both proteins mediate novel chromatin recruitment pathways that are central in our understanding of human disease mechanisms. We also discuss how disease mutations affect DNMT3A and DNMT3B oligomerisation, a process that is poorly understood in the context of whole proteins in cells. This dissection of de novo DNMT function using disease-causing mutations provides a paradigm of how genetics and biochemistry can synergise to drive our understanding of the mechanisms through which chromatin misregulation causes human disease.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2059-2075"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493963","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

The exocyst in context. 外囊的背景

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-10-30 DOI: 10.1042/BST20231401

Sasha Meek, Altair C Hernandez, Baldomero Oliva, Oriol Gallego

{"title":"The exocyst in context.","authors":"Sasha Meek, Altair C Hernandez, Baldomero Oliva, Oriol Gallego","doi":"10.1042/BST20231401","DOIUrl":"10.1042/BST20231401","url":null,"abstract":"The exocyst is a hetero-octameric complex involved in the exocytosis arm of cellular trafficking. Specifically, it tethers secretory vesicles to the plasma membrane, but it is also a main convergence point for many players of exocytosis: regulatory proteins, motor proteins, lipids and Soluble N-ethylmaleimide-sensitive factor Attachment Protein Receptor (SNARE) proteins are all connected physically by the exocyst. Despite extensive knowledge about its structure and interactions, the exocyst remains an enigma precisely because of its increasingly broad and flexible role across the exocytosis process. To solve the molecular mechanism of such a multi-tasking complex, dynamical structures with self, other proteins, and environment should be described. And to do this, interrogation within contexts increasingly close to native conditions is needed. Here we provide a perspective on how different experimental contexts have been used to study the exocyst, and those that could be used in the future. This review describes the structural breakthroughs on the isolated in vitro exocyst, followed by the use of membrane reconstitution assays for revealing in vitro exocyst functionality. Next, it moves to in situ cell contexts, reviewing imaging techniques that have been, and that ideally could be, used to look for near-native structure and organization dynamics. Finally, it looks at the exocyst structure in situ within evolutionary contexts, and the potential of structure prediction therein. From in vitro, to in situ, cross-context investigation of exocyst structure has begun, and will be critical for functional mechanism elucidation.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2113-2122"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387605","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

Suppression of double-stranded RNA sensing in cancer: molecular mechanisms and therapeutic potential. 抑制癌症中的双链 RNA 感知：分子机制和治疗潜力。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-10-30 DOI: 10.1042/BST20230727

Addison A Young, Holly E Bohlin, Jackson R Pierce, Kyle A Cottrell

{"title":"Suppression of double-stranded RNA sensing in cancer: molecular mechanisms and therapeutic potential.","authors":"Addison A Young, Holly E Bohlin, Jackson R Pierce, Kyle A Cottrell","doi":"10.1042/BST20230727","DOIUrl":"10.1042/BST20230727","url":null,"abstract":"Immunotherapy has emerged as a therapeutic option for many cancers. For some tumors, immune checkpoint inhibitors show great efficacy in promoting anti-tumor immunity. However, not all tumors respond to immunotherapies. These tumors often exhibit reduced inflammation and are resistant to checkpoint inhibitors. Therapies that turn these 'cold' tumors 'hot' could improve the efficacy and applicability of checkpoint inhibitors, and in some cases may be sufficient on their own to promote anti-tumor immunity. One strategy to accomplish this goal is to activate innate immunity pathways within the tumor. Here we describe how this can be accomplished by activating double-stranded RNA (dsRNA) sensors. These sensors evolved to detect and respond to dsRNAs arising from viral infection but can also be activated by endogenous dsRNAs. A set of proteins, referred to as suppressors of dsRNA sensing, are responsible for preventing sensing 'self' dsRNA and activating innate immunity pathways. The mechanism of action of these suppressors falls into three categories: (1) Suppressors that affect mature RNAs through editing, degradation, restructuring, or binding. (2) Suppressors that affect RNA processing. (3) Suppressors that affect RNA expression. In this review we highlight suppressors that function through each mechanism, provide examples of the effects of disrupting those suppressors in cancer cell lines and tumors, and discuss the therapeutic potential of targeting these proteins and pathways.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2035-2045"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103970","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

Do tunneling nanotubes drive chemoresistance in solid tumors and other malignancies? 隧道纳米管是否会驱动实体瘤和其他恶性肿瘤的化疗抗药性？

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-08-28 DOI: 10.1042/BST20231364

Akshat Sarkari, Emil Lou

{"title":"Do tunneling nanotubes drive chemoresistance in solid tumors and other malignancies?","authors":"Akshat Sarkari, Emil Lou","doi":"10.1042/BST20231364","DOIUrl":"10.1042/BST20231364","url":null,"abstract":"Intercellular communication within the tumor microenvironment (TME) is essential for establishing, mediating, and synchronizing cancer cell invasion and metastasis. Cancer cells, individually and collectively, react at the cellular and molecular levels to insults from standard-of-care treatments used to treat patients with cancer. One form of cell communication that serves as a prime example of cellular phenotypic stress response is a type of cellular protrusion called tunneling nanotubes (TNTs). TNTs are ultrafine, actin-enriched contact-dependent forms of membrane protrusions that facilitate long distance cell communication through transfer of various cargo, including genetic materials, mitochondria, proteins, ions, and various other molecules. In the past 5-10 years, there has been a growing body of evidence that implicates TNTs as a novel mechanism of cell-cell communication in cancer that facilitates and propagates factors that drive or enhance chemotherapeutic resistance in a variety of cancer cell types. Notably, recent literature has highlighted the potential of TNTs to serve as cellular conduits and mediators of drug and nanoparticle delivery. Given that TNTs have also been shown to form in vivo in a variety of tumor types, disrupting TNT communication within the TME provides a novel strategy for enhancing the cytotoxic effect of existing chemotherapies while suppressing this form of cellular stress response. In this review, we examine current understanding of interplay between cancer cells occurring via TNTs, and even further, the implications of TNT-mediated tumor-stromal cross-talk and the potential to enhance chemoresistance. We then examine tumor microtubes, an analogous cell protrusion heavily implicated in mediating treatment resistance in glioblastoma multiforme, and end with a brief discussion of the effects of radiation and other emerging treatment modalities on TNT formation.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1757-1764"},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733482","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

Satellite cell dynamics during skeletal muscle hypertrophy. 骨骼肌肥大过程中卫星细胞的动态变化

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-08-28 DOI: 10.1042/BST20240201

Tolulope P Saliu, Jensen Goh, Gyumin Kang, Benjamin I Burke, Ahmed Ismaeel, John J McCarthy

引用次数: 0

Understanding pyrethrin biosynthesis: toward and beyond natural pesticide overproduction. 了解除虫菊酯的生物合成：走向并超越天然杀虫剂的过度生产。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-08-28 DOI: 10.1042/BST20240213

Kazuhiko Matsuda

引用次数: 0

Molecular aspects of Interleukin-36 cytokine activation and regulation. 白细胞介素-36 细胞因子激活和调节的分子方面。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-08-28 DOI: 10.1042/BST20230548

Jennifer Keller, James R O' Siorain, Thomas M Kündig, Mark Mellett

{"title":"Molecular aspects of Interleukin-36 cytokine activation and regulation.","authors":"Jennifer Keller, James R O' Siorain, Thomas M Kündig, Mark Mellett","doi":"10.1042/BST20230548","DOIUrl":"10.1042/BST20230548","url":null,"abstract":"Interleukin-36 (IL-36) cytokines are structurally similar to other Interleukin-1 superfamily members and are essential to convey inflammatory responses at epithelial barriers including the skin, lung, and gut. Due to their potent effects on immune cells, IL-36 cytokine activation is regulated on multiple levels, from expression and activation to receptor binding. Different IL-36 isoforms convey specific responses as a consequence of particular danger- or pathogen-associated molecular patterns. IL-36 expression and activation are regulated by exogenous pathogens, including fungi, viruses and bacteria but also by endogenous factors such as antimicrobial peptides or cytokines. Processing of IL-36 into potent bioactive forms is necessary for host protection but can elevate tissue damage. Indeed, exacerbated IL-36 signalling and hyperactivation are linked to the pathogenesis of diseases such as plaque and pustular psoriasis, emphasising the importance of understanding the molecular aspects regulating IL-36 activation. Here, we summarise facets of the electrochemical properties, regulation of extracellular cleavage by various proteases and receptor signalling of the pro-inflammatory and anti-inflammatory IL-36 family members. Additionally, this intriguing cytokine subfamily displays many characteristics that are unique from prototypical members of the IL-1 family and these key distinctions are outlined here.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1591-1604"},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465973","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

Roles for PMP22 in Schwann cell cholesterol homeostasis in health and disease. PMP22 在健康和疾病中的许旺细胞胆固醇稳态中的作用

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-08-28 DOI: 10.1042/BST20231359

Katherine M Stefanski, Mason C Wilkinson, Charles R Sanders

引用次数: 0

TDP-43 in nuclear condensates: where, how, and why. 核凝聚物中的 TDP-43：在哪里、如何以及为什么。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-08-28 DOI: 10.1042/BST20231447

Ruaridh Lang, Rachel E Hodgson, Tatyana A Shelkovnikova

引用次数: 0

Cytokinin and reproductive shoot architecture: bigger and better? 细胞分裂素和生殖芽结构：越大越好？

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2024-08-28 DOI: 10.1042/BST20231565

Catriona H Walker, Tom Bennett

{"title":"Cytokinin and reproductive shoot architecture: bigger and better?","authors":"Catriona H Walker, Tom Bennett","doi":"10.1042/BST20231565","DOIUrl":"10.1042/BST20231565","url":null,"abstract":"Cytokinin (CK) is a key plant hormone, but one whose effects are often misunderstood, partly due to reliance on older data from before the molecular genetic age of plant science. In this mini-review, we examine the role of CK in controlling the reproductive shoot architecture of flowering plants. We begin with a long overdue re-examination of the role of CK in shoot branching, and discuss the relatively paucity of genetic evidence that CK does play a major role in this process. We then examine the role of CK in determining the number of inflorescences, flowers, fruit and seed that plants initiate during reproductive development, and how these are arranged in space and time. The genetic evidence for a major role of CK in controlling these processes is much clearer, and CK has profound effects in boosting the size and number of most reproductive structures. Conversely, the attenuation of CK levels during the reproductive phase likely contributes to reduced organ size seen later in flowering, and the ultimate arrest of inflorescence meristems during end-of-flowering. We finish by discussing how this information can potentially be used to improve crop yields.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1885-1893"},"PeriodicalIF":3.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854618","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