Title | GSK-3β phosphorylation of DHX33 leads to its ubiquitination mediated protein degradation |
Author | |
Corresponding Author | Zhang,Yandong |
Publication Years | 2023
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DOI | |
Source Title | |
ISSN | 0898-6568
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EISSN | 1873-3913
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Volume | 101 |
Abstract | DHX33 is a member of DEAD/H box protein family, and is involved in both RNA and DNA metabolism. It plays diverse roles in multiple cellular activities. DHX33 overexpression has been found to promote the development of many human cancers. However, the underlying mechanism to explain its high expression in cancer cells remains incompletely resolved. In this study, with both human cancer cell lines and normal fibroblasts, we found glycogen synthase kinase 3β (GSK-3β) regulates DHX33 protein stability. This is through its direct phosphorylation of DHX33 on T482, which triggers ubiquitination mediate protein degradation. We further identified one of the major ubiquitination sites of DHX33 to be on its N-terminal K94, a critical residue previously found to be important and highly conserved for ATP binding and helicase activity. Our study for the first time reveals an important upstream regulator, GSK-3β, as a critical kinase to phosphorylate DHX33 at the post-translational level leading to its degradation. Moreover, cancer cells have frequent GSK3β deactivation to disrupt this signaling cascade. Therefore, DHX33 is stabilized in many cancer cells as compared to normal cells. Our study unveils an important post-translational regulation of DHX33 in cells and further unveils a novel mechanism for DHX33 overexpression in cancer cells. |
Keywords | |
URL | [Source Record] |
Indexed By | |
Language | English
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SUSTech Authorship | Others
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WOS Research Area | Cell Biology
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WOS Subject | Cell Biology
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WOS Accession No | WOS:000926463200002
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Publisher | |
ESI Research Field | MOLECULAR BIOLOGY & GENETICS
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Scopus EID | 2-s2.0-85143202035
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Data Source | Scopus
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Citation statistics |
Cited Times [WOS]:2
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Document Type | Journal Article |
Identifier | http://kc.sustech.edu.cn/handle/2SGJ60CL/416457 |
Department | Department of Biology 生命科学学院 |
Affiliation | 1.Shenzhen KeYe Life Technologies, Co., Ltd, Shenzhen, Guangdong 518000, China 2.Shenzhen KeYe Life Technologies, Co., Ltd, Shenzhen, Guangdong 518000, China; Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China 3.Department of Biology,Southern University of Science and Technology,Shenzhen,518055,China |
Recommended Citation GB/T 7714 |
Zhang,Yandong,Chen,Shiyun,Peng,Cheng. GSK-3β phosphorylation of DHX33 leads to its ubiquitination mediated protein degradation[J]. CELLULAR SIGNALLING,2023,101.
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APA |
Zhang,Yandong,Chen,Shiyun,&Peng,Cheng.(2023).GSK-3β phosphorylation of DHX33 leads to its ubiquitination mediated protein degradation.CELLULAR SIGNALLING,101.
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MLA |
Zhang,Yandong,et al."GSK-3β phosphorylation of DHX33 leads to its ubiquitination mediated protein degradation".CELLULAR SIGNALLING 101(2023).
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