Acetylation of PHF5A Modulates Stress Responses and Colorectal Carcinogenesis through Alternative Splicing-Mediated Upregulation of KDM3A

被引：58

作者：

Wang, Zhe ^{[1
]}

Yang, Xin ^{[1
]}

Liu, Cheng ^{[2
]}

Li, Xin ^{[3
]}

Zhang, Buyu ^{[4
]}

Wang, Bo ^{[5
]}

Zhang, Yu ^{[1
]}

Song, Chen ^{[1
]}

Zhang, Tianzhuo ^{[1
]}

Liu, Minghui ^{[1
]}

Liu, Boya ^{[1
]}

Ren, Mengmeng ^{[1
]}

Jiang, Hongpeng ^{[5
]}

Zou, Junhua ^{[1
]}

Liu, Xiaoyun ^{[4
]}

Zhang, Hongquan ^{[2
]}

Zhu, Wei-Guo ^{[6
]}

Yin, Yuxin ^{[7
]}

Zhang, Zhang ^{[8
]}

Gu, Wei ^{[9
]}

Luo, Jianyuan ^{[1
,10
]}

机构：

[1] Peking Univ, Hlth Sci Ctr, Ctr Med Genet, Dept Med Genet, Beijing 100191, Peoples R China

[2] Peking Univ, Hlth Sci Ctr, Dept Anat Histol & Embryol, Beijing 100191, Peoples R China

[3] Peking Union Med Coll Hosp, Dept Allergy, Beijing 100730, Peoples R China

[4] Peking Univ, Hlth Sci Ctr, Dept Microbiol, Beijing 100191, Peoples R China

[5] Peking Univ, Peoples Hosp, Dept Gastroenterol Surg, Beijing 100044, Peoples R China

[6] Shenzhen Univ, Sch Med, Dept Biochem & Mol Biol, Shenzhen 518060, Peoples R China

[7] Peking Univ, Hlth Sci Ctr, Inst Syst Biomed, Beijing 100191, Peoples R China

[8] Jingjie PTM Biolab Hangzhou Co Ltd, Hangzhou 310018, Zhejiang, Peoples R China

[9] Columbia Univ, Inst Canc Genet, New York, NY 10032 USA

[10] Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing Key Lab Prot Posttranslat Modificat & Cel, Beijing 100191, Peoples R China

来源：

MOLECULAR CELL | 2019年 / 74卷 / 06期

基金：

中国国家自然科学基金;

关键词：

GENE-EXPRESSION; CANCER; AUTOPHAGY; JMJD1A; REQUIREMENT; METABOLISM; MECHANISMS; GROWTH; JHDM2A;

D O I：

10.1016/j.molcel.2019.04.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Alternative pre-mRNA-splicing-induced post-transcriptional gene expression regulation is one of the pathways for tumors maintaining proliferation rates accompanying the malignant phenotype under stress. Here, we uncover a list of hyperacetylated proteins in the context of acutely reduced Acetyl-CoA levels under nutrient starvation. PHF5A, a component of U2 snRNPs, can be acetylated at lysine 29 in response to multiple cellular stresses, which is dependent on p300. PHF5A acetylation strengthens the interaction among U2 snRNPs and affects global pre-mRNA splicing pattern and extensive gene expression. PHF5A hyperacetylation-induced alternative splicing stabilizes KDM3A mRNA and promotes its protein expression. Pathologically, PHF5A K29 hyperacetylation and KDM3A upregulation axis are correlated with poor prognosis of colon cancer. Our findings uncover a mechanism of an anti-stress pathway through which acetylation on PHF5A promotes the cancer cells' capacity for stress resistance and consequently contributes to colon carcinogenesis.

引用

页码：1250 / +

页数：20

共 1 条

[1] SIRT7-Induced PHF5A Decrotonylation Regulates Aging Progress Through Alternative Splicing-Mediated Downregulation of CDK2
Yu, Ai Qing
Wang, Jie
Jiang, Shi Tao
Yuan, Li Qun
Ma, Hai Yan
Hu, Yi Min
Han, Xing Min
Tan, Li Ming
Wang, Zhi Xiao
[J]. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2021, 9

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