title: PHF20 is an effector protein of p53 double lysine methylation that stabilizes and activates p53.
abstract: PHF20 is a multidomain protein and subunit of a lysine acetyltransferase complex that acetylates histone H4 and p53 but whose function is unclear. Using biochemical, biophysical and cellular approaches, we determined that PHF20 is a direct regulator of p53. A Tudor domain in PHF20 recognized p53 dimethylated at Lys370 or Lys382 and a homodimeric form of this Tudor domain could associate with the two dimethylated sites on p53 with enhanced affinity, indicating a multivalent interaction. Association with PHF20 promotes stabilization and activation of p53 by diminishing Mdm2-mediated p53 ubiquitylation and degradation. PHF20 contributes to upregulation of p53 in response to DNA damage, and ectopic expression of PHF20 in different cell lines leads to phenotypic changes that are hallmarks of p53 activation. Overall our work establishes that PHF20 functions as an effector of p53 methylation that stabilizes and activates p53.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Gaofeng
authors.initials: G
authors.lastname: Cui
authors.forename: Sungman
authors.initials: S
authors.lastname: Park
authors.forename: Aimee I
authors.initials: AI
authors.lastname: Badeaux
authors.forename: Donghwa
authors.initials: D
authors.lastname: Kim
authors.forename: Joseph
authors.initials: J
authors.lastname: Lee
authors.forename: James R
authors.initials: JR
authors.lastname: Thompson
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kaneko
authors.forename: Zengqiang
authors.initials: Z
authors.lastname: Yuan
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Botuyan
authors.forename: Mark T
authors.initials: MT
authors.lastname: Bedford
authors.forename: Jin Q
authors.initials: JQ
authors.lastname: Cheng
authors.forename: Georges
authors.initials: G
authors.lastname: Mer
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004249:DNA Damage; D004268:DNA-Binding Proteins; D055785:Gene Knockdown Techniques; D006801:Humans; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D008745:Methylation; D008958:Models, Molecular; D055503:Protein Multimerization; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D015854:Up-Regulation
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C440091:PHF20 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D008239:Lysine