Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression.

Détails

ID Serval
serval:BIB_3B75745BC4CC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression.
Périodique
Molecular and cellular biology
Auteur⸱e⸱s
Yokoyama A., Wang Z., Wysocka J., Sanyal M., Aufiero D.J., Kitabayashi I., Herr W., Cleary M.L.
ISSN
0270-7306
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
24
Numéro
13
Pages
5639-5649
Langue
anglais
Résumé
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 1 (HCF-1), a transcriptional coregulator, and the related HCF-2, both of which specifically interact with a conserved binding motif in the MLL(N) (p300) subunit of MLL 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.
Mots-clé
Cell Line, Tumor, DNA-Binding Proteins, Gene Expression Regulation, Histone-Lysine N-Methyltransferase, Homeodomain Proteins, Host Cell Factor C1, Humans, K562 Cells, Leukemia, Macromolecular Substances, Myeloid-Lymphoid Leukemia Protein, Protein Binding, Protein Methyltransferases, Proteins, Proto-Oncogene Proteins, Proto-Oncogenes, Saccharomyces cerevisiae Proteins, Transcription Factors
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 15:36
Dernière modification de la notice
20/08/2019 13:31
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