期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 24, 期 13, 页码 5639-5649出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.24.13.5639-5649.2004
关键词
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资金
- NCI NIH HHS [CA55029, P01 CA013106, CA13106, R01 CA055029] Funding Source: Medline
- NIGMS NIH HHS [GM54598, R01 GM054598] Funding Source: Medline
MLL (for mixed-lineage leukemia) is a proto-oncogene that is mutated in a variety of human leukemias. Its product, a homolog of Drosophila melanogaster trithorax, displays intrinsic histone methyltransferase activity and functions genetically to maintain embryonic Hox gene expression. Here we report the biochemical purification of MLL and demonstrate that it associates with a cohort of proteins shared with the yeast and human SET1 histone methyltransferase complexes, including a homolog of Ash2, another Trx-G group protein. Two other members of the novel MLL complex identified here are host cell factor I (HCF-1), a transcriptional coregulator, and the related HCF-2, both of which specifically interact with a conserved binding motif in the MLLN (p300) subunit of MILL and provide a potential mechanism for regulating its antagonistic transcriptional properties. Menin, a product of the MEN1 tumor suppressor gene, is also a component of the 1-MDa MLL complex. Abrogation of menin expression phenocopies loss of MLL and reveals a critical role for menin in the maintenance of Hox gene expression. Oncogenic mutant forms of MLL retain an ability to interact with menin but not other identified complex components. These studies link the menin tumor suppressor protein with the MLL histone methyltransferase machinery, with implications for Hox gene expression in development and leukemia pathogenesis.
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