Mitochondria-targeted Catalase induced cell malignant transformation by the downregulation of p53 protein stability via USP28/miR-200b/PP2A-Cα axis

doi:10.1016/j.abb.2024.110047

科研成果详情

题名	Mitochondria-targeted Catalase induced cell malignant transformation by the downregulation of p53 protein stability via USP28/miR-200b/PP2A-Cα axis
作者	Chaowei Wen1; Chao Huang 2; Xin Liao 2; Zhefeng Luo 1; Chuanshu Huang3
发表日期	2024-06-04
发表期刊	Archives of biochemistry and biophysics 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	PP2A USP28 cell transformation mitochondrial catalase p53
其他关键词	MESSENGER-RNA ; C-JUN ; CANCER ; PROMOTES ; UBIQUITINATION ; PROLIFERATION ; DEGRADATION ; METASTASIS ; INVASION
摘要	Antioxidants exert a paradoxical influence on cancer prevention. The latest explanation for this paradox is the different target sites of antioxidants. However, it remains unclear how mitochondria-targeted antioxidants trigger specific p53-dependent pathways in malignant transformation models. Our study revealed that overexpression of mitochondria-targeted catalase (mCAT) instigated such malignant transformation via mouse double minute 2 homolog (MDM2) -mediated p53 degradation. In mouse epithelial JB6 Cl41 cells, the stable expression of mCAT resulted in MDM2-mediated p53 degradation, unlike in catalase-overexpressed Cl41 cells. Further, we demonstrated that mCAT overexpression unregulated ubiquitin-specific protease 28 (USP28) expression, which in turn stabilized c-Jun protein levels. This alteration initiated the activation of the miR-200b promoter transcription activity and a subsequent increase in miR-200b expression. Furthermore, elevated miR-200b levels then promoted its binding to the 3'-untranslated region of protein phosphatase 2A catalytic subunit (PP2A-C) α-isoform mRNA, consequently resulting in PP2A-C protein downregulation. This cascade of events ultimately contributed to increased MDM2 phosphorylation and p53 protein degradation. Thus, the mCAT overexpression triggers MDM2/p53-dependent malignant transformation through USP28/miR-200b/PP2A-Cα pathway, which may provide a new information of understanding mitochondria-targeted antioxidant facilitates the progression to the tumorigenic state.
资助项目	Foundation of China [NSFC81773391, NSFC81702530]; Oujiang Research Project [OJQD2022006]
出版者	ELSEVIER SCIENCE INC
ISSN	0003-9861
EISSN	1096-0384
卷号	758
DOI	10.1016/j.abb.2024.110047
页数	10
WOS类目	Biochemistry & Molecular Biology ; Biophysics
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
WOS记录号	WOS:001259280100001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	38844154
SCOPUSEID	2-s2.0-85196194809
通讯作者地址	[Luo, Zhefeng;Huang, Chuanshu]Wenzhou Med Univ, Sch Lab Med & Life Sci, Key Lab Lab Med, Minist Educ, Wenzhou 325035, Zhejiang, Peoples R China.
Scopus学科分类	Biophysics;Biochemistry;Molecular Biology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/215103
专题	检验医学院（生命科学学院、生物学实验教学中心）其他_瓯江实验室
作者单位	1.Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.; 2.Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.; 3.Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China. Electronic address: huangchuanshu@wmu.edu.cn.
第一作者单位	检验医学院（生命科学学院、生物学实验教学中心）; 瓯江实验室
通讯作者单位	检验医学院（生命科学学院、生物学实验教学中心）
第一作者的第一单位	检验医学院（生命科学学院、生物学实验教学中心）
推荐引用方式 GB/T 7714	Chaowei Wen,Chao Huang,Xin Liao,et al. Mitochondria-targeted Catalase induced cell malignant transformation by the downregulation of p53 protein stability via USP28/miR-200b/PP2A-Cα axis[J]. Archives of biochemistry and biophysics,2024,758.
APA	Chaowei Wen, Chao Huang, Xin Liao, Zhefeng Luo, & Chuanshu Huang. (2024). Mitochondria-targeted Catalase induced cell malignant transformation by the downregulation of p53 protein stability via USP28/miR-200b/PP2A-Cα axis. Archives of biochemistry and biophysics, 758.
MLA	Chaowei Wen,et al."Mitochondria-targeted Catalase induced cell malignant transformation by the downregulation of p53 protein stability via USP28/miR-200b/PP2A-Cα axis".Archives of biochemistry and biophysics 758(2024).