Coronin7 forms a novel E3 ubiquitin ligase complex to promote the degradation of the anti-proliferative protein Tob.
Tob belongs to the anti-proliferative Tob/BTG family. The level of Tob throughout the cell cycle is regulated by the SCF (Skp1/Cullin/F-box protein)(Skp2) ubiquitin ligase (E3) complex. Here, we show that Coronin7 (CRN7) is also involved in Tob degradation. We identified CRN7 as a Tob-interacting molecule. A sequence containing two of the six WD motifs in the middle of CRN7 was responsible for the interaction. CRN7 enhanced the polyubiquitination of Tob in vitro, and overexpression of CRN7 promoted proteasome-dependent degradation of Tob. Furthermore, CRN7 interacted with Cullin1 and Roc1 to form a novel SCF-like E3 complex, suggesting that Tob protein is regulated by multiple ubiquitination machineries.
Division of Oncology, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Makoto
M
Watanabe
Toru
T
Suzuki
Minsoo
M
Kim
Yoshinori
Y
Abe
Yutaka
Y
Yoshida
Sumio
S
Sugano
Tadashi
T
Yamamoto
D000596:Amino Acids / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
D000596:Amino Acids; D002352:Carrier Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D008840:Microfilament Proteins; C479529:RBX1 protein, human; D025521:Tumor Suppressor Proteins; C072061:coronin proteins; D044767:Ubiquitin-Protein Ligases