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.
You
Jianxin
J
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Wang
Min
M
Aoki
Tsutomu
T
Tamura
Taka-aki
TA
Pickart
Cecile M
CM
D000818:Animals; D019556:COS Cells / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D020134:Catalytic Domain; D006801:Humans; D008025:Ligases / Q000737:chemistry / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D025821:Polyubiquitin; D046988:Proteasome Endopeptidase Complex; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000378:metabolism; D013379:Substrate Specificity; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases
C486317:CAND1 protein, human; C485649:CAND2 protein, human; D002352:Carrier Proteins; D009124:Muscle Proteins; D021122:Protein Subunits; D014157:Transcription Factors; D025821:Polyubiquitin; D044767:Ubiquitin-Protein Ligases; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D008025:Ligases