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PKB-mediated PHF20 phosphorylation on Ser291 is required for p53 function in DNA damage
Yuwen Li1, Jisoo Park, Longzhen Piao
1Department of Pharmacology, Metabolic Diseases and Cell Signaling Laboratory, Cancer Research Institute, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, 301-131, South Korea.
Cellular Signalling
|September 15, 2012
Summary
PHD finger protein 20 (PHF20), a cancer-associated protein, is phosphorylated by protein kinase B (PKB). This phosphorylation inhibits p53 induction after DNA damage, impacting cancer development.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- PHD finger protein 20 (PHF20) is implicated in various cancers, including glioma, lung, colon, and ovarian cancers.
- PHF20's precise function in tumorigenesis remains largely uncharacterized.
- Protein kinase B (PKB) is involved in cellular signaling pathways crucial for cancer development.
Purpose of the Study:
- To investigate the functional relationship between PHF20 and PKB.
- To elucidate the role of PHF20 phosphorylation by PKB in cancer signaling pathways.
- To determine the impact of this interaction on p53-mediated gene expression.
Main Methods:
- In vitro and in vivo phosphorylation assays to confirm PKB-PHF20 interaction.
- UV-induced DNA damage models to assess p53 and p21 responses.
- Western blot analysis using specific antibodies against PHF20 and phosphorylated PKB (pPKB S473).
- Analysis of human cancer tissues to map these molecular events.
Main Results:
- PHF20 contains consensus phosphorylation sites for PKB and is directly phosphorylated by PKB at Ser291.
- PKB-mediated PHF20 phosphorylation inhibits the induction of p53 following UV-induced DNA damage.
- This inhibition leads to reduced p21 transcriptional activity, a key regulator of cell cycle arrest.
- The phosphorylation events were observed in various human cancer tissues.
Conclusions:
- PHF20 is a novel substrate for PKB, and its phosphorylation plays a significant role in tumorigenesis.
- PKB-mediated phosphorylation of PHF20 regulates the p53 signaling pathway, contributing to cancer development.
- Targeting the PKB-PHF20 interaction may offer a novel therapeutic strategy for cancers associated with this pathway.
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