ARF-dependent regulation of ATM and p53 associated KZNF (Apak) protein activity in response to oncogenic stress

Shan Wang; Chunyan Tian; Guichun Xing; Mei Gao; Wenjuan Jiao; Tingting Xiao; Yuxin Yin; Fuchu He; Lingqiang Zhang

doi:10.1016/j.febslet.2010.08.015

ARF-dependent regulation of ATM and p53 associated KZNF (Apak) protein activity in response to oncogenic stress

FEBS Lett. 2010 Sep 24;584(18):3909-15. doi: 10.1016/j.febslet.2010.08.015. Epub 2010 Aug 14.

Authors

Shan Wang¹, Chunyan Tian, Guichun Xing, Mei Gao, Wenjuan Jiao, Tingting Xiao, Yuxin Yin, Fuchu He, Lingqiang Zhang

Affiliation

¹ State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.

PMID: 20713054
DOI: 10.1016/j.febslet.2010.08.015

Abstract

The KRAB-type zinc-finger protein Apak (ATM and p53 associated KZNF protein) specifically suppresses p53-mediated apoptosis. Upon DNA damage, Apak is phosphorylated and inhibited by ATM kinase, resulting in p53 activation. However, how Apak is regulated in response to oncogenic stress remains unknown. Here we show that upon oncogene activation, Apak is inhibited in the tumor suppressor ARF-dependent but ATM-independent manner. Oncogene-induced ARF protein directly interacts with Apak and competes with p53 to bind to Apak, resulting in Apak dissociation from p53. Thus, Apak is differentially regulated in the ARF and ATM-dependent manner in response to oncogenic stress and DNA damage, respectively.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis Regulatory Proteins / biosynthesis*
Ataxia Telangiectasia Mutated Proteins
Carrier Proteins / biosynthesis*
Cell Cycle Proteins / metabolism*
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p16 / antagonists & inhibitors
Cyclin-Dependent Kinase Inhibitor p16 / genetics
Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
DNA Damage*
DNA-Binding Proteins / metabolism*
Humans
Protein Serine-Threonine Kinases / metabolism*
RNA Interference
Stress, Physiological*
Tumor Suppressor Protein p53 / metabolism*
Tumor Suppressor Proteins / metabolism*
Zinc Fingers*

Substances

Apoptosis Regulatory Proteins
Carrier Proteins
Cell Cycle Proteins
Cyclin-Dependent Kinase Inhibitor p16
DNA-Binding Proteins
Tumor Suppressor Protein p53
Tumor Suppressor Proteins
ZNF420 protein, human
ATM protein, human
Ataxia Telangiectasia Mutated Proteins
Protein Serine-Threonine Kinases