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CDK9 inhibitors reactivate p53 by downregulating iASPP

Cell Signal. 2020-03; 
Wu J, Liang Y, Tan Y, Tang Y, Song H, Wang Z, Li Y, Lu M.
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Catalog Antibody … Primary antibodies and compounds were purchased from the following companies: DO1 (ab1101, abcam), β-actin (A00702, Genscript), PUMA (12,450, Cell Signaling Technology), p21 (2947, Cell Signaling Technology), MDM2 (ab38618, abcam), PIG3 (ab96819, abcam … Get A Quote

摘要

Loss of p53's tumor-suppressive function, either via TP53 mutation or hyperactive p53 inhibitory proteins, is one of the most frequent events in the development of human cancer. Here, we describe a strategy of pharmacologically inhibiting iASPP, a negative regulator of p53, to restore wild-type p53's tumor-suppressive function. iASPP knockdown in the colon cancer cell line HCT116 efficiently promoted p53's transcriptional activity and induced p53-dependent cell death, suggesting a key role for iASPP in silencing p53 in this cell line. Screening of a preclinical and clinical drug library using isogenic HCT116 cell models revealed that cyclin-dependent kinase 9 (CDK9) inhibitors preferentially inhibit p53+/+, rat... More

关键词

CDK9 inhibitor; Concurrent inhibition; MDM2; iASPP; p53 reactivation