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

被引：19

作者：

Yuan, Lin ^{[1
,2
,3
]}

Tian, Chunyan ^{[2
,3
]}

Wang, Hongye ^{[1
,2
,3
]}

Song, Shanshan ^{[2
,3
,4
,5
]}

Li, Deyang ^{[2
]}

Xing, Guichun ^{[2
,3
]}

Yin, Yuxin ^{[6
]}

He, Fuchu ^{[2
,3
]}

Zhang, Lingqiang ^{[1
,2
,3
]}

机构：

[1] Anhui Med Univ, Dept Biochem & Mol Biol, Hefei 230032, Anhui, Peoples R China

[2] Beijing Inst Radiat Med, Beijing Proteome Res Ctr, State Key Lab Prote, Beijing 100850, Peoples R China

[3] Natl Engn Res Ctr Prot Drugs, Beijing 100850, Peoples R China

[4] Peking Union Med Coll, Beijing 100005, Peoples R China

[5] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Med Genet, Beijing 100005, Peoples R China

[6] Peking Univ, Sch Basic Med Sci, Dept Pathol, Beijing 100191, Peoples R China

来源：

EMBO REPORTS | 2012年 / 13卷 / 04期

基金：

北京市自然科学基金;

关键词：

p53; p53AIP1; transcriptional regulation; apoptosis; Apak; ZINC-FINGER PROTEIN; P53-DEPENDENT APOPTOSIS; DISEASE;

D O I：

10.1038/embor.2012.10

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 TCTTN2-30 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.

引用

页码：363 / 370

页数：8

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