KRAB-type Zinc-finger Protein Apak Specifically Regulates P53-dependent Apoptosis

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2009 Apr 21

PMID 19377469

Citations 61

Authors

Chunyan Tian

Guichun Xing

Ping Xie

Kefeng Lu

Jing Nie

Jian Wang

Li Li

Mei Gao

Lingqiang Zhang

Fuchu He

Affiliations

Soon will be listed here.

Abstract

Only a few p53 regulators have been shown to participate in the selective control of p53-mediated cell cycle arrest or apoptosis. How p53-mediated apoptosis is negatively regulated remains largely unclear. Here we report that Apak (ATM and p53-associated KZNF protein), a Krüppel-associated box (KRAB)-type zinc-finger protein, binds directly to p53 in unstressed cells, specifically downregulates pro-apoptotic genes, and suppresses p53-mediated apoptosis by recruiting KRAB-box-associated protein (KAP)-1 and histone deacetylase 1 (HDAC1) to attenuate the acetylation of p53. Apak inhibits p53 activity by interacting with ATM, a previously identified p53 activator. In response to stress, Apak is phosphorylated by ATM and dissociates from p53, resulting in activation of p53 and induction of apoptosis. These findings revealed Apak to be a negative regulator of p53-mediated apoptosis and showed the dual role of ATM in p53 regulation.

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