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.
authors.affiliation: Department 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.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Li
authors.forename: Jisoo
authors.initials: J
authors.lastname: Park
authors.forename: Longzhen
authors.initials: L
authors.lastname: Piao
authors.forename: Gyeyeong
authors.initials: G
authors.lastname: Kong
authors.forename: Yongbaek
authors.initials: Y
authors.lastname: Kim
authors.forename: Kyeong Ah
authors.initials: KA
authors.lastname: Park
authors.forename: Tiejun
authors.initials: T
authors.lastname: Zhang
authors.forename: Janghee
authors.initials: J
authors.lastname: Hong
authors.forename: Gang Min
authors.initials: GM
authors.lastname: Hur
authors.forename: Jeong Ho
authors.initials: JH
authors.lastname: Seok
authors.forename: Seung-Won
authors.initials: SW
authors.lastname: Choi
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
authors.forename: Brian A
authors.initials: BA
authors.lastname: Hemmings
authors.forename: Derek P
authors.initials: DP
authors.lastname: Brazil
authors.forename: Seon-Hwan
authors.initials: SH
authors.lastname: Kim
authors.forename: Jongsun
authors.initials: J
authors.lastname: Park
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000528:radiation effects*; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D007328:Insulin; C440091:PHF20 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D012694:Serine; D051057:Proto-Oncogene Proteins c-akt