Seo-Hyun Choi, Su-Yeon Cho, Sun Young Park, Man-Wook Hur
{"title":"癌细胞中p53状态对原癌基因ZBTB7A表达的翻译后调控:hsp90依赖性稳定与p53- klhl20泛素蛋白酶体降解","authors":"Seo-Hyun Choi, Su-Yeon Cho, Sun Young Park, Man-Wook Hur","doi":"10.1016/j.bbagrm.2023.194931","DOIUrl":null,"url":null,"abstract":"<div><p><span><span>ZBTB7A overexpressed in many human cancers is a major oncogenic driver. ZBTB7A promotes tumorigenesis by regulating transcription of the genes involved in cell survival and proliferation, apoptosis, invasion, and migration/metastasis. One unresolved issue is the mechanism underlying the aberrant overexpression of ZBTB7A in cancer cells. Interestingly, inhibition of HSP90 decreased ZBTB7A expression in a variety of human cancer cells. ZBTB7A interacts with and is stabilized by HSP90. Inhibition of HSP90 by 17-AAG resulted in p53-dependent </span>proteolysis<span> of ZBTB7A via increased p53 expression and upregulation of the CUL3-dependent E3 ubiquitin ligase<span>, KLHL20. Down-regulation of ZBTB7A resulted in the derepression of a major negative regulator of cell cycle progression, </span></span></span><em>p21/CDKN1A</em>. We discovered a new function of p53 regulating ZBTB7A expression through KLHL20-E3 ligase and proteasomal protein degradation system.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 2","pages":"Article 194931"},"PeriodicalIF":2.6000,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Post-translational regulation of proto-oncogene ZBTB7A expression by p53 status in cancer cells: HSP90-dependent stabilization vs. p53-KLHL20-ubiquitin proteasomal degradation\",\"authors\":\"Seo-Hyun Choi, Su-Yeon Cho, Sun Young Park, Man-Wook Hur\",\"doi\":\"10.1016/j.bbagrm.2023.194931\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span><span>ZBTB7A overexpressed in many human cancers is a major oncogenic driver. ZBTB7A promotes tumorigenesis by regulating transcription of the genes involved in cell survival and proliferation, apoptosis, invasion, and migration/metastasis. One unresolved issue is the mechanism underlying the aberrant overexpression of ZBTB7A in cancer cells. Interestingly, inhibition of HSP90 decreased ZBTB7A expression in a variety of human cancer cells. ZBTB7A interacts with and is stabilized by HSP90. Inhibition of HSP90 by 17-AAG resulted in p53-dependent </span>proteolysis<span> of ZBTB7A via increased p53 expression and upregulation of the CUL3-dependent E3 ubiquitin ligase<span>, KLHL20. Down-regulation of ZBTB7A resulted in the derepression of a major negative regulator of cell cycle progression, </span></span></span><em>p21/CDKN1A</em>. We discovered a new function of p53 regulating ZBTB7A expression through KLHL20-E3 ligase and proteasomal protein degradation system.</p></div>\",\"PeriodicalId\":55382,\"journal\":{\"name\":\"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms\",\"volume\":\"1866 2\",\"pages\":\"Article 194931\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2023-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1874939923000263\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1874939923000263","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Post-translational regulation of proto-oncogene ZBTB7A expression by p53 status in cancer cells: HSP90-dependent stabilization vs. p53-KLHL20-ubiquitin proteasomal degradation
ZBTB7A overexpressed in many human cancers is a major oncogenic driver. ZBTB7A promotes tumorigenesis by regulating transcription of the genes involved in cell survival and proliferation, apoptosis, invasion, and migration/metastasis. One unresolved issue is the mechanism underlying the aberrant overexpression of ZBTB7A in cancer cells. Interestingly, inhibition of HSP90 decreased ZBTB7A expression in a variety of human cancer cells. ZBTB7A interacts with and is stabilized by HSP90. Inhibition of HSP90 by 17-AAG resulted in p53-dependent proteolysis of ZBTB7A via increased p53 expression and upregulation of the CUL3-dependent E3 ubiquitin ligase, KLHL20. Down-regulation of ZBTB7A resulted in the derepression of a major negative regulator of cell cycle progression, p21/CDKN1A. We discovered a new function of p53 regulating ZBTB7A expression through KLHL20-E3 ligase and proteasomal protein degradation system.
期刊介绍：
BBA Gene Regulatory Mechanisms includes reports that describe novel insights into mechanisms of transcriptional, post-transcriptional and translational gene regulation. Special emphasis is placed on papers that identify epigenetic mechanisms of gene regulation, including chromatin, modification, and remodeling. This section also encompasses mechanistic studies of regulatory proteins and protein complexes; regulatory or mechanistic aspects of RNA processing; regulation of expression by small RNAs; genomic analysis of gene expression patterns; and modeling of gene regulatory pathways. Papers describing gene promoters, enhancers, silencers or other regulatory DNA regions must incorporate significant functions studies.
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