title: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui Province 230032, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.forename: Chunyan
authors.initials: C
authors.lastname: Tian
authors.forename: Hongye
authors.initials: H
authors.lastname: Wang
authors.forename: Shanshan
authors.initials: S
authors.lastname: Song
authors.forename: Deyang
authors.initials: D
authors.lastname: Li
authors.forename: Guichun
authors.initials: G
authors.lastname: Xing
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Yin
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D001667:Binding, Competitive; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D007438:Introns / Q000235:genetics*; D008969:Molecular Sequence Data; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; C414742:P53AIP1 protein, human; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; C540923:ZNF420 protein, human