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PMID:9537414

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Citation

Cui, X, De Vivo, I, Slany, R, Miyamoto, A, Firestein, R and Cleary, ML (1998) Association of SET domain and myotubularin-related proteins modulates growth control. Nat. Genet. 18:331-7

Abstract

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.

Links

PubMed Online version:10.1038/ng0498-331

Keywords

3T3 Cells/cytology; 3T3 Cells/metabolism; Amino Acid Sequence; Animals; Binding Sites; Carrier Proteins/genetics; Carrier Proteins/physiology; Cell Differentiation/genetics; Cell Differentiation/physiology; Cell Division/physiology; Cell Transformation, Neoplastic/genetics; Chromosomal Proteins, Non-Histone; Conserved Sequence/genetics; Conserved Sequence/physiology; Histone Chaperones; Humans; Intracellular Signaling Peptides and Proteins; Mice; Molecular Sequence Data; Myocardium/cytology; Myocardium/metabolism; Phosphoric Monoester Hydrolases/metabolism; Protein Binding; Protein Structure, Tertiary; Protein Tyrosine Phosphatases/genetics; Protein Tyrosine Phosphatases/physiology; Protein Tyrosine Phosphatases, Non-Receptor; Proteins/chemistry; Proteins/isolation & purification; Proteins/metabolism; Sequence Homology, Amino Acid; Transcription Factors

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:MTMR5

NOT|enables

GO:0016791: phosphatase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MTM1

involved_in

GO:0006470: protein dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MTM1

enables

GO:0004721: phosphoprotein phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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