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Proteolytic targeting of transcriptional regulator TIP120B by a HECT domain E3 ligase.

Ubiquitin-protein ligases (E3s) of the HECT family share a conserved catalytic region that is homologous to the E6-AP C terminus. The HECT domain defines a large E3 family, but only a handful of these enzymes have been defined with respect to substrate specificity or biological function. We showed previously that the C-terminal domain of one family member, KIAA10, catalyzes the assembly of polyubiquitin chains, whereas the N-terminal domain binds to proteasomes in vitro (You, J., and Pickart, C. M. (2001) J. Biol. Chem. 276, 19871-19878). We show here that KIAA10 also associates with proteasomes within cells but that this association probably involves additional contacts with proteasome subunits other than the one (S2/Rpn1) identified in our previous work. We report that the N-domain of KIAA10 also mediates an association with TIP120B (TATA-binding protein-interacting protein 120B), a putative transcriptional regulator. Biochemical and co-transfection studies revealed that TIP120B, but not the closely related protein TIP120A, is a specific substrate of KIAA10 in vitro and within C2C12 myoblasts but not in Cos-1 cells. KIAA10 and TIP120B are both highly expressed in human skeletal muscle, suggesting that KIAA10 may regulate TIP120B homeostasis specifically in this tissue.

Pubmed ID: 12692129


  • You J
  • Wang M
  • Aoki T
  • Tamura TA
  • Pickart CM


The Journal of biological chemistry

Publication Data

June 27, 2003

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK46984

Mesh Terms

  • Animals
  • COS Cells
  • Carrier Proteins
  • Catalytic Domain
  • Humans
  • Ligases
  • Muscle Proteins
  • Myoblasts
  • Peptide Hydrolases
  • Polyubiquitin
  • Proteasome Endopeptidase Complex
  • Protein Structure, Tertiary
  • Protein Subunits
  • Substrate Specificity
  • Transcription Factors
  • Ubiquitin-Protein Ligases