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

Nat Genet. 1998 Apr;18(4):331-7. doi: 10.1038/ng0498-331.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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
  • DNA-Binding Proteins
  • 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

Substances

  • Carrier Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Histone Chaperones
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • SBF1 protein, human
  • SET protein, human
  • Transcription Factors
  • Phosphoric Monoester Hydrolases
  • Protein Tyrosine Phosphatases
  • Protein Tyrosine Phosphatases, Non-Receptor
  • myotubularin

Associated data

  • GENBANK/U93181