A subset of mixed lineage leukemia proteins has plant homeodomain (PHD)-mediated E3 ligase activity

Jingya Wang, Andrew G. Muntean, Laura Wu, Jay L. Hess

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The mixed lineage leukemia protein MLL1 contains four highly conserved plant homeodomain (PHD) fingers, which are invariably deleted in oncogenic MLL1 fusion proteins in human leukemia. Here we show that the second PHD finger (PHD2) of MLL1 is an E3 ubiquitin ligase in the presence of the E2-conjugating enzyme CDC34. This activity is conserved in the second PHD finger of MLL4, the closest homolog to MLL1 but not in MLL2 or MLL3. Mutation of PHD2 leads to MLL1 stabilization, as well as increased transactivation ability and MLL1 recruitment to the target gene loci, suggesting that PHD2 negatively regulates MLL1 activity.

Original languageEnglish (US)
Pages (from-to)43410-43416
Number of pages7
JournalJournal of Biological Chemistry
Volume287
Issue number52
DOIs
StatePublished - Dec 21 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'A subset of mixed lineage leukemia proteins has plant homeodomain (PHD)-mediated E3 ligase activity'. Together they form a unique fingerprint.

  • Cite this