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QSER1 preserves the suppressive status of the pro-apoptotic genes to prevent apoptosis

Authors :
Xiru Zhao
Ke Fang
Xiaoxu Liu
Ruihuan Yao
Min Wang
Fanfan Li
Shaohua Hao
Jingjing He
Yan Wang
Menghan Fan
Wei Huang
Yiping Li
Chun Gao
Chengqi Lin
Zhuojuan Luo
Source :
Cell Death & Differentiation. 30:779-793
Publication Year :
2022
Publisher :
Springer Science and Business Media LLC, 2022.

Abstract

Activation of the pro-apoptotic genes by the p53 family is a critical step in induction of apoptosis. However, the molecular signaling underlying their suppression remains largely unknown. Here, we report a general role of QSER1 in preventing apoptosis. QSER1 is widely up-regulated in multiple cancers, and its up-regulation correlates with poor clinic outcomes. QSER1 knockdown significantly promotes apoptosis in both p53 wild type and mutant cancer cells. Interestingly, we show that QSER1 and p53 occupy distinct cis-regulatory regions in a common subset of the pro-apoptotic genes, and function antagonistically to maintain their proper expression. Furthermore, we identify a key regulatory DNA element named QSER1 binding site in PUMA (QBP). Deletion of QBP de-represses PUMA and induces apoptosis. Mechanistically, QSER1 functions together with SIN3A to suppress PUMA in a p53-dependent and -independent manner, suggesting that QSER1 inhibition might be a potential therapeutic strategy to induce apoptosis in cancers.

Subjects

Subjects :
Cell Biology
Molecular Biology

Details

ISSN :
14765403 and 13509047
Volume :
30
Database :
OpenAIRE
Journal :
Cell Death & Differentiation
Accession number :
edsair.doi.dedup.....a1c7e6c53002832d6e87fdeb1204ab18
Full Text :
https://doi.org/10.1038/s41418-022-01085-x