期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 287, 期 52, 页码 43410-43416出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.423855
关键词
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资金
- National Institutes of Health [K99 CA158136-01, R01 CA151425]
- American Society of Hematology Scholar Award
- Leukemia and Lymphoma Society Specialized Center of Research grant
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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