title: Identification of Akt interaction protein PHF20/TZP that transcriptionally regulates p53.
abstract: Akt regulates a diverse array of cellular functions, including cell survival, proliferation, differentiation, and metabolism. Although a number of molecules have been identified as upstream regulators and downstream targets of Akt, the mechanisms by which Akt regulates these cellular processes remain elusive. Here, we demonstrate that a novel transcription factor, PHF20/TZP (referring to Tudor and zinc finger domain containing protein), binds to Akt and induces p53 expression at the transcription level. Knockdown of PHF20 significantly reduces p53. PHF20 inhibits cell growth, DNA synthesis, and cell survival. Akt phosphorylates PHF20 at Ser(291) in vitro and in vivo, which results in its translocation from the nucleus to the cytoplasm and attenuation of PHF20 function. These data indicate that PHF20 is a substrate of Akt and plays a role in Akt cell survival/growth signaling.
authors.affiliation: Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
authors.forename: Sungman
authors.initials: S
authors.lastname: Park
authors.forename: Donghwa
authors.initials: D
authors.lastname: Kim
authors.forename: Han C
authors.initials: HC
authors.lastname: Dan
authors.forename: Huihua
authors.initials: H
authors.lastname: Chen
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Testa
authors.forename: Jin Q
authors.initials: JQ
authors.lastname: Cheng
mesh_terms: D021581:Active Transport, Cell Nucleus; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D016384:Consensus Sequence; D004268:DNA-Binding Proteins; D006801:Humans; D059372:Nucleotide Motifs; D010766:Phosphorylation; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002843:Chromatin; D004268:DNA-Binding Proteins; C440091:PHF20 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D012694:Serine; D051057:Proto-Oncogene Proteins c-akt