3p8d | pdb_00003p8d
Crystal structure of the second Tudor domain of human PHF20 (homodimer form)
Structural highlights
FunctionPHF20_HUMAN Methyllysine-binding protein, component of the MOF histone acetyltransferase protein complex. Not required for maintaining the global histone H4 'Lys-16' acetylation (H4K16ac) levels or locus specific histone acetylation, but instead works downstream in transcriptional regulation of MOF target genes (By similarity). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. Contributes to methyllysine-dependent p53/TP53 stabilization and up-regulation after DNA damage.[1] [2] Publication Abstract from PubMedPHF20 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. PHF20 is an effector protein of p53 double lysine methylation that stabilizes and activates p53.,Cui G, Park S, Badeaux AI, Kim D, Lee J, Thompson JR, Yan F, Kaneko S, Yuan Z, Botuyan MV, Bedford MT, Cheng JQ, Mer G Nat Struct Mol Biol. 2012 Aug 5. doi: 10.1038/nsmb.2353. PMID:22864287[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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