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.
Cui
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X
Department of Pathology, Stanford University Medical Center, California 94305, USA.
De Vivo
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I
Slany
R
R
Miyamoto
A
A
Firestein
R
R
Cleary
M L
ML
D016475:3T3 Cells / Q000166:cytology / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone; D017124:Conserved Sequence / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C111446:SBF1 protein, human; C513473:SET protein, human; D014157:Transcription Factors; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin