Literature DB >> 23129768

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

Jingya Wang1, Andrew G Muntean, Laura Wu, Jay L Hess.   

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.

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Year:  2012        PMID： 23129768      PMCID： PMC3527928          DOI： 10.1074/jbc.M112.423855

Source DB:  PubMed          Journal:  J Biol Chem        ISSN： 0021-9258            Impact factor:   5.157


  35 in total

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