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

doi:10.1016/j.cellsig.2012.09.009

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.

Original language	English
Pages (from-to)	74–84
Number of pages	11
Journal	Cellular Signalling
Volume	25
Issue number	1
DOIs	https://doi.org/10.1016/j.cellsig.2012.09.009
Publication status	Published - Jan 2013

ASJC Scopus subject areas

Cell Biology

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PKB-mediated PHF20 phosphorylation on Ser291 is required for p53 function in DNA damage
This is the author’s version of a work that was accepted for publication in Cellular Signalling. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Cellular Signalling, VOL25, ISSUE1, 01/2013
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@article{68bc3bf7f515471d88cb1250986d17be,

title = "PKB-mediated PHF20 phosphorylation on Ser291 is required for p53 function in DNA damage",

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. ",

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

year = "2013",

month = jan,

doi = "10.1016/j.cellsig.2012.09.009",

language = "English",

volume = "25",

pages = "74–84",

journal = "Cellular Signalling",

publisher = "Elsevier Inc.",

number = "1",

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T1 - PKB-mediated PHF20 phosphorylation on Ser291 is required for p53 function in DNA damage

AU - Li, Yuwen

AU - Park, Jisoo

AU - Piao, Longzhen

AU - Kong, Gyeyeong

AU - Kim, Yongbaek

AU - Park, Kyeong Ah

AU - Zhang, Tiejun

AU - Hong, Janghee

AU - Hur, Gang Min

AU - Seok, Jeong Ho

AU - Choi, Seung-Won

AU - Yoo, Byong Chul

AU - Hemmings, Brian A.

AU - Brazil, Derek

AU - Kim, Seon-Hwan

AU - Park, Jongsun

PY - 2013/1

Y1 - 2013/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.cellsig.2012.09.009

DO - 10.1016/j.cellsig.2012.09.009

M3 - Article

VL - 25

SP - 74

EP - 84

JO - Cellular Signalling

JF - Cellular Signalling

IS - 1

ER -

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

Abstract

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