ARF-dependent regulation of ATM and p53 associated KZNF (Apak) protein activity in response to oncogenic stress.
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.
Mesh Terms:
Apoptosis Regulatory Proteins, Carrier Proteins, Cell Cycle Proteins, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p16, DNA Damage, DNA-Binding Proteins, Humans, Protein-Serine-Threonine Kinases, RNA Interference, Stress, Physiological, Tumor Suppressor Protein p53, Tumor Suppressor Proteins, Zinc Fingers
Apoptosis Regulatory Proteins, Carrier Proteins, Cell Cycle Proteins, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p16, DNA Damage, DNA-Binding Proteins, Humans, Protein-Serine-Threonine Kinases, RNA Interference, Stress, Physiological, Tumor Suppressor Protein p53, Tumor Suppressor Proteins, Zinc Fingers
FEBS Lett.
Date: Sep. 24, 2010
PubMed ID: 20713054
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