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Apak competes with p53 for direct binding to intron 1 of p53AIP1 to regulate apoptosis
Author(s) -
Yuan Lin,
Tian Chunyan,
Wang Hongye,
Song Shanshan,
Li Deyang,
Xing Guichun,
Yin Yuxin,
He Fuchu,
Zhang Lingqiang
Publication year - 2012
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2012.10
Subject(s) - intron , apoptosis , microbiology and biotechnology , biology , genetics , computational biology , gene
The KRAB‐type zinc‐finger protein Apak was recently identified as a negative regulator of p53‐mediated apoptosis. However, the mechanism of this selective regulation is not fully understood. Here, we show that Apak recognizes the TCTTN 2−30 TTGT consensus sequence through its zinc‐fingers. This sequence is specifically found in intron 1 of the proapoptotic p53 target gene p53AIP1 and largely overlaps with the p53‐binding sequence. Apak competes with p53 for binding to this site to inhibit p53AIP1 expression. Upon DNA damage, Apak dissociates from the DNA, which abolishes its inhibitory effect on p53‐mediated apoptosis.