{"title":"KLHL20 及其在细胞稳态中的作用:新视角和治疗潜力。","authors":"","doi":"10.1016/j.lfs.2024.123041","DOIUrl":null,"url":null,"abstract":"<div><p>Ubiquitin ligases are proteins with the ability to trigger non-degradative signaling or proteasomal destruction by attracting substrates and facilitating ubiquitin transfer onto target proteins. Over the years, there has been a continuous discovery of new ubiquitin ligases, and Kelch-like protein 20 (KLHL20) is one of the most recent discoveries that have several biological roles which include its role in ubiquitin ligase activities. KLHL20 binds as a substrate component of ubiquitin ligase Cullin3 (Cul3). Several substrates for ubiquitin ligases (KLHL20 based) have been reported, these include Unc-51 Like Autophagy Activating Kinase 1 (ULK1), promyelocytic leukemia (PML), and Death Associated Protein Kinase 1 (DAPK1). KLHL20 shows multiple cell functions linked to several human diseases through ubiquitination of these substrates. Current literature shows that KLHL20 ubiquitin ligase regulates malignancies in humans and also suggests how important it is to develop regulating agents for tumour-suppressive KLHL20 to prevent tumourigenesis, Recent research has highlighted its potential therapeutic implications in several areas. In oncology, KLHL20's regulatory role in protein degradation pathways suggests that its targeting could offer novel strategies for cancer treatment by modulating the stability of proteins involved in tumour growth and survival. In neurodegenerative diseases, KLHL20's function in maintaining protein homeostasis positions it as a potential target for therapies aimed at managing protein aggregation and cellular stress. Here, we review the functions of KLHL20 during the carcinogenesis process, looking at its role in cancer progression, and regulation of ubiquitination events mediated by KLHL20 in human cancers, as well as its potential therapeutic interventions.</p></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"KLHL20 and its role in cell homeostasis: A new perspective and therapeutic potential\",\"authors\":\"\",\"doi\":\"10.1016/j.lfs.2024.123041\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Ubiquitin ligases are proteins with the ability to trigger non-degradative signaling or proteasomal destruction by attracting substrates and facilitating ubiquitin transfer onto target proteins. Over the years, there has been a continuous discovery of new ubiquitin ligases, and Kelch-like protein 20 (KLHL20) is one of the most recent discoveries that have several biological roles which include its role in ubiquitin ligase activities. KLHL20 binds as a substrate component of ubiquitin ligase Cullin3 (Cul3). Several substrates for ubiquitin ligases (KLHL20 based) have been reported, these include Unc-51 Like Autophagy Activating Kinase 1 (ULK1), promyelocytic leukemia (PML), and Death Associated Protein Kinase 1 (DAPK1). KLHL20 shows multiple cell functions linked to several human diseases through ubiquitination of these substrates. Current literature shows that KLHL20 ubiquitin ligase regulates malignancies in humans and also suggests how important it is to develop regulating agents for tumour-suppressive KLHL20 to prevent tumourigenesis, Recent research has highlighted its potential therapeutic implications in several areas. In oncology, KLHL20's regulatory role in protein degradation pathways suggests that its targeting could offer novel strategies for cancer treatment by modulating the stability of proteins involved in tumour growth and survival. In neurodegenerative diseases, KLHL20's function in maintaining protein homeostasis positions it as a potential target for therapies aimed at managing protein aggregation and cellular stress. Here, we review the functions of KLHL20 during the carcinogenesis process, looking at its role in cancer progression, and regulation of ubiquitination events mediated by KLHL20 in human cancers, as well as its potential therapeutic interventions.</p></div>\",\"PeriodicalId\":18122,\"journal\":{\"name\":\"Life sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2024-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Life sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0024320524006313\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0024320524006313","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
KLHL20 and its role in cell homeostasis: A new perspective and therapeutic potential
Ubiquitin ligases are proteins with the ability to trigger non-degradative signaling or proteasomal destruction by attracting substrates and facilitating ubiquitin transfer onto target proteins. Over the years, there has been a continuous discovery of new ubiquitin ligases, and Kelch-like protein 20 (KLHL20) is one of the most recent discoveries that have several biological roles which include its role in ubiquitin ligase activities. KLHL20 binds as a substrate component of ubiquitin ligase Cullin3 (Cul3). Several substrates for ubiquitin ligases (KLHL20 based) have been reported, these include Unc-51 Like Autophagy Activating Kinase 1 (ULK1), promyelocytic leukemia (PML), and Death Associated Protein Kinase 1 (DAPK1). KLHL20 shows multiple cell functions linked to several human diseases through ubiquitination of these substrates. Current literature shows that KLHL20 ubiquitin ligase regulates malignancies in humans and also suggests how important it is to develop regulating agents for tumour-suppressive KLHL20 to prevent tumourigenesis, Recent research has highlighted its potential therapeutic implications in several areas. In oncology, KLHL20's regulatory role in protein degradation pathways suggests that its targeting could offer novel strategies for cancer treatment by modulating the stability of proteins involved in tumour growth and survival. In neurodegenerative diseases, KLHL20's function in maintaining protein homeostasis positions it as a potential target for therapies aimed at managing protein aggregation and cellular stress. Here, we review the functions of KLHL20 during the carcinogenesis process, looking at its role in cancer progression, and regulation of ubiquitination events mediated by KLHL20 in human cancers, as well as its potential therapeutic interventions.
期刊介绍:
Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed.
The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.