期刊
CELL DEATH AND DIFFERENTIATION
卷 30, 期 3, 页码 779-793出版社
SPRINGERNATURE
DOI: 10.1038/s41418-022-01085-x
关键词
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QSER1 plays a general role in preventing apoptosis and is up-regulated in multiple cancers. It functions antagonistically with p53 to maintain the expression of pro-apoptotic genes and suppresses PUMA in a p53-dependent and -independent manner. Inhibition of QSER1 might be a potential therapeutic strategy to induce apoptosis in cancer cells.
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.
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