中文版 | English
Title

CLP36 promotes p53 deficient sarcoma progression through suppression of atrophin-1 interacting protein-4 (AIP-4)-dependent degradation of YAP1

Author
Corresponding AuthorGuo,Ling; Wu,Chuanyue
Publication Years
2022
DOI
Source Title
ISSN
1838-7640
Volume12Issue:11Pages:5051-5068
Abstract

Background: p53 deficiency is a key causal factor for tumor development and progression. p53 acts in this process through, at least in part, cooperation with YAP1 but the underlying molecular mechanism is incompletely understood. In this paper, we show that CLP36, an actinin-binding cytoskeletal protein, links p53 deficiency to up-regulation of YAP1 expression and sarcoma progression. Methods: Immunohistochemical staining and Western blotting were used to investigate the effect of p53 deficiency on CLP36 expression in sarcoma tissues and cells. Furthermore, molecular, cellular, and genetic knockout and knockdown approaches were employed to investigate the functions of CLP36 in regulation of sarcoma cell behavior in culture and tumor growth in mice. Finally, biochemical approaches were used to investigate the molecular mechanism by which CLP36 regulates the malignant behavior of p53 deficient sarcoma cells. Results: We have found that the expression of CLP36 is up-regulated in response to loss of p53 in sarcoma tissues and cells. Depletion of CLP36 inhibited malignant behavior of p53 deficient sarcoma cells. Furthermore, knockout of CLP36 in mice markedly inhibited p53 deficiency-induced tumorigenesis and improved the survival of the p53 deficient mice. Mechanistically, CLP36 promoted p53 deficiency-induced tumorigenesis through inhibition of E3 ligase atrophin-1 interacting protein-4 (AIP-4)-dependent proteasomal degradation of YAP1 and consequently increase of YAP1 expression. Conclusions: Our results reveal a crucial role of CLP36 in linking p53 deficiency to up-regulation of YAP1 expression and sarcoma progression. Our findings suggest that therapeutic targeting the CLP36/YAP1 signaling axis may provide an effective strategy for alleviation of p53 deficient sarcoma progression.

Keywords
URL[Source Record]
Indexed By
Language
English
SUSTech Authorship
First ; Corresponding
Funding Project
National Key R&D Program of China[2019FYA090060000] ; Natural Science Foundation of Guangdong Province[2017B030301018] ; Shenzhen Innovation Committee of Science and Technology[
WOS Research Area
Research & Experimental Medicine
WOS Subject
Medicine, Research & Experimental
WOS Accession No
WOS:000830834100001
Publisher
Scopus EID
2-s2.0-85133676974
Data Source
Web of Science
Citation statistics
Cited Times [WOS]:0
Document TypeJournal Article
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/355939
DepartmentDepartment of Biology
生命科学学院
前沿与交叉科学研究院
南方科技大学医学院
Affiliation
1.Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research,Shenzhen Key Laboratory of Cell Microenvironment,Department of Biology,Academy for Advanced Interdisciplinary Studies,Southern University of Science and Technology,Shenzhen,518055,China
2.Department of Clinical Oncology,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Hong Kong,999077,Hong Kong
3.Department of Medicine,University of California,,San Diego,La Jolla,92093,United States
4.Department of Pathology,School of Medicine,University of Pittsburgh,Pittsburgh,15261,United States
First Author AffilicationDepartment of Biology;  School of Medicine;  Academy for Advanced Interdisciplinary Studies;  School of Life Sciences
Corresponding Author AffilicationDepartment of Biology;  School of Medicine;  Academy for Advanced Interdisciplinary Studies;  School of Life Sciences
First Author's First AffilicationDepartment of Biology;  School of Medicine;  Academy for Advanced Interdisciplinary Studies;  School of Life Sciences
Recommended Citation
GB/T 7714
Lu,Yixuan,Mu,Yongxin,Chen,Ju,et al. CLP36 promotes p53 deficient sarcoma progression through suppression of atrophin-1 interacting protein-4 (AIP-4)-dependent degradation of YAP1[J]. Theranostics,2022,12(11):5051-5068.
APA
Lu,Yixuan,Mu,Yongxin,Chen,Ju,Guan,Xinyuan,Guo,Ling,&Wu,Chuanyue.(2022).CLP36 promotes p53 deficient sarcoma progression through suppression of atrophin-1 interacting protein-4 (AIP-4)-dependent degradation of YAP1.Theranostics,12(11),5051-5068.
MLA
Lu,Yixuan,et al."CLP36 promotes p53 deficient sarcoma progression through suppression of atrophin-1 interacting protein-4 (AIP-4)-dependent degradation of YAP1".Theranostics 12.11(2022):5051-5068.
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