Format

Send to

Choose Destination
See comment in PubMed Commons below
Nat Struct Mol Biol. 2012 Sep;19(9):916-24. doi: 10.1038/nsmb.2353. Epub 2012 Aug 5.

PHF20 is an effector protein of p53 double lysine methylation that stabilizes and activates p53.

Author information

1
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.

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.

PMID:
22864287
PMCID:
PMC3454513
DOI:
10.1038/nsmb.2353
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center