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Apak competes with p53 for direct binding to intron 1 of p53AIP1 to regulate apoptosis.

ABSTRACT: 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 TCTTN2?30TTGT 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.

SUBMITTER: Yuan L 

PROVIDER: S-EPMC3321147 | biostudies-other | 2012 Apr

REPOSITORIES: biostudies-other

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Apak competes with p53 for direct binding to intron 1 of p53AIP1 to regulate apoptosis.

Yuan Lin L   Tian Chunyan C   Wang Hongye H   Song Shanshan S   Li Deyang D   Xing Guichun G   Yin Yuxin Y   He Fuchu F   Zhang Lingqiang L  

EMBO reports 20120401 4

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 TCTTN2−30TTGT 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  ...[more]