Coronin7 forms a novel E3 ubiquitin ligase complex to promote the degradation of the anti-proliferative protein Tob |
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Authors: | Watanabe Makoto Suzuki Toru Kim Minsoo Abe Yoshinori Yoshida Yutaka Sugano Sumio Yamamoto Tadashi |
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Affiliation: | aDivision of Oncology, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan;bDivision of Bacterial Infection, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan;cDepartment of Medical Genome Science, Graduate Frontier Science, University of Tokyo, Tokyo 108-8639, Japan |
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Abstract: | 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.Structured summaryCullin1physically interacts with CRN7: shown by anti tag coimmunoprecipitation (view interaction)Roc1physically interacts with CRN7: shown by anti tag coimmunoprecipitation (view interaction)CRN7physically interacts with Tob1: shown by anti tag coimmunoprecipitation (view interaction)CDC34physically interacts with CRN7: shown by anti tag coimmunoprecipitation (view interaction)Tob1 and CRN7colocalize: shown by fluorescence microscopy (view interaction)Elongin Bphysically interacts with CRN7: shown by anti tag coimmunoprecipitation (view interaction)Elongin Cphysically interacts with CRN7: shown by anti tag coimmunoprecipitation (view interaction)Tob1physically interacts with CRN7: shown by two hybrid (view interaction) |
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Keywords: | Tob Coronin7 Ubiquitination E3 ligase |
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