PKB-mediated PHF20 phosphorylation on Ser291 is required for p53 function in DNA damage

Yuwen Li, Jisoo Park, Longzhen Piao, Gyeyeong Kong, Yongbaek Kim, Kyeong Ah Park, Tiejun Zhang, Janghee Hong, Gang Min Hur, Jeong Ho Seok, Seung-Won Choi, Byong Chul Yoo, Brian A. Hemmings, Derek Brazil, Seon-Hwan Kim, Jongsun Park

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Abstract

PHD finger protein 20 (PHF20) is a transcription factor, which was originally identified in glioma patients. PHF20 appears to be a novel antigen in glioma, and has also termed glioma-expressed antigen 2. PHF20 is thought to contribute to the development of cancers, including glioblastoma, lung cancer, colon cancer and ovarian cancer. However, little is known about the function of PHF20 in various cancers. Here we report that PHF20 contains two consensus sites for protein kinase B (PKB) phosphorylation (RxRxxS/T). PKB can directly phosphorylate PHF20 on Ser291 in vitro and in vivo. It has been shown that PKB participates in the tumor suppressor p53 regulated gene expression program and has a direct effect on p21 regulation after DNA damage. UV-induced DNA damage results in accumulation of p53 and PKB activation. Interestingly, PKB-mediated PHF20 phosphorylation led to an inhibition of p53 induction following UV treatment, leading to the reduction of p21 transcriptional activity. Using anti PHF20 and anti pPKB (S473) antibodies, these events were mapped in various human cancer tissues. Taken together, these data suggest that PHF20 is a novel substrate for PKB and its phosphorylation by PKB plays an important role in tumorigenesis via regulating of p53 mediated signaling. © 2012 Elsevier Inc.
Original languageEnglish
Pages (from-to)74–84
Number of pages11
JournalCellular Signalling
Volume25
Issue number1
DOIs
Publication statusPublished - Jan 2013

ASJC Scopus subject areas

  • Cell Biology

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    Li, Y., Park, J., Piao, L., Kong, G., Kim, Y., Park, K. A., Zhang, T., Hong, J., Hur, G. M., Seok, J. H., Choi, S-W., Yoo, B. C., Hemmings, B. A., Brazil, D., Kim, S-H., & Park, J. (2013). PKB-mediated PHF20 phosphorylation on Ser291 is required for p53 function in DNA damage. Cellular Signalling, 25(1), 74–84. https://doi.org/10.1016/j.cellsig.2012.09.009