中文版 | English
Title

GSK-3β phosphorylation of DHX33 leads to its ubiquitination mediated protein degradation

Author
Corresponding AuthorZhang,Yandong
Publication Years
2023
DOI
Source Title
ISSN
0898-6568
EISSN
1873-3913
Volume101
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
SUSTech Authorship
Others
WOS Research Area
Cell Biology
WOS Subject
Cell Biology
WOS Accession No
WOS:000926463200002
Publisher
ESI Research Field
MOLECULAR BIOLOGY & GENETICS
Scopus EID
2-s2.0-85143202035
Data Source
Scopus
Citation statistics
Cited Times [WOS]:2
Document TypeJournal Article
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/416457
DepartmentDepartment 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.
APA
Zhang,Yandong,Chen,Shiyun,&Peng,Cheng.(2023).GSK-3β phosphorylation of DHX33 leads to its ubiquitination mediated protein degradation.CELLULAR SIGNALLING,101.
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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