Association of SET domain and myotubularin-related proteins modulates growth control.

Several proteins that contribute to epigenetic mechanisms of gene regulation contain a characteristic motif of unknown function called the SET (Suvar3-9, Enhancer-of-zeste, Trithorax) domain. We have demonstrated that SET domains mediate highly conserved interactions with a specific family of proteins that display similarity with dual-specificity phosphatases (dsPTPases). These include myotubularin, ...
the gene of which is mutated in a subset of patients with X-linked myotubular myopathy, and Sbf1, a newly isolated homologue of myotubularin. In contrast with myotubularin, Sbf1 lacks a functional catalytic domain which dephosphorylates phospho-tyrosine and serine-containing peptides in vitro. Competitive interference of endogenous SET domain-dsPTPase interactions by forced expression of Sbf1 induced oncogenic transformation of NIH 3T3 fibroblasts and impaired the in vitro differentiation of C2 myoblast cells. We conclude that myotubularin-type phosphatases link SET-domain containing components of the epigenetic regulatory machinery with signalling pathways involved in growth and differentiation.
Mesh Terms:
3T3 Cells, Amino Acid Sequence, Animals, Binding Sites, Carrier Proteins, Cell Differentiation, Cell Division, Cell Transformation, Neoplastic, Chromosomal Proteins, Non-Histone, Conserved Sequence, Histone Chaperones, Humans, Intracellular Signaling Peptides and Proteins, Mice, Molecular Sequence Data, Myocardium, Phosphoric Monoester Hydrolases, Protein Binding, Protein Structure, Tertiary, Protein Tyrosine Phosphatases, Protein Tyrosine Phosphatases, Non-Receptor, Proteins, Sequence Homology, Amino Acid, Transcription Factors
Nat. Genet.
Date: Apr. 01, 1998
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