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

Gaofeng Cui, Sungman Park, Aimee I. Badeaux, Donghwa Kim, Joseph Lee, James R. Thompson, Fei Yan, Satoshi Kaneko, Zengqiang Yuan, Maria Victoria Botuyan, Mark T. Bedford, Jin Q. Cheng, Georges Mer

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)916-924
Number of pages9
JournalNature Structural and Molecular Biology
Volume19
Issue number9
DOIs
StatePublished - Sep 2012

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Methylation
Lysine
Ubiquitination
Protein Subunits
Histones
DNA Damage
Proteins
Up-Regulation
Cell Line
Tudor Domain
Lysine Acetyltransferases
Ectopic Gene Expression

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

PHF20 is an effector protein of p53 double lysine methylation that stabilizes and activates p53. / Cui, Gaofeng; Park, Sungman; Badeaux, Aimee I.; Kim, Donghwa; Lee, Joseph; Thompson, James R.; Yan, Fei; Kaneko, Satoshi; Yuan, Zengqiang; Botuyan, Maria Victoria; Bedford, Mark T.; Cheng, Jin Q.; Mer, Georges.

In: Nature Structural and Molecular Biology, Vol. 19, No. 9, 09.2012, p. 916-924.

Research output: Contribution to journalArticle

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 2012, 'PHF20 is an effector protein of p53 double lysine methylation that stabilizes and activates p53', Nature Structural and Molecular Biology, vol. 19, no. 9, pp. 916-924. https://doi.org/10.1038/nsmb.2353
Cui, Gaofeng ; Park, Sungman ; Badeaux, Aimee I. ; Kim, Donghwa ; Lee, Joseph ; Thompson, James R. ; Yan, Fei ; Kaneko, Satoshi ; Yuan, Zengqiang ; Botuyan, Maria Victoria ; Bedford, Mark T. ; Cheng, Jin Q. ; Mer, Georges. / PHF20 is an effector protein of p53 double lysine methylation that stabilizes and activates p53. In: Nature Structural and Molecular Biology. 2012 ; Vol. 19, No. 9. pp. 916-924.
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