Degradation of Tob1 mediated by SCFSkp2-dependent ubiquitination

Yoshihiro Hiramatsu, Kyoko Kitagawa, Toru Suzuki, Chiharu Uchida, Takayuki Hattori, Hirotoshi Kikuchi, Toshiaki Oda, Shigetsugu Hatakeyama, Keiichi I. Nakayama, Tadashi Yamamoto, Hiroyuki Konno, Masatoshi Kitagawa

研究成果: ジャーナルへの寄稿記事

43 引用 (Scopus)


Tob1, a member of the Tob/BTG family, is involved in the control of G 1-S progression by suppressing cyclin D1 expression and acts as a tumor suppressor gene. Tob1 was reported to have a quick turnover through the ubiquitin-proteasome pathway, but proteins involved in this process are still unknown. We showed that Skp2, a substrate-targeting subunit of the SCF (Skp1/Cul1/F-box protein) ubiquitin ligase complex, was involved in ubiquitin-dependent degradation of Tob1. Skp2 interacted with Tob1 and facilitated ubiquitination of Tob1 in intact cells as well as in vitro. Skp2 mutants without the F-box or leucine rich repeat were not able to bind to Tob1 and did not enhance ubiquitination of Tob1. Tob1 was stabilized in both Skp2-/- mouse fibroblasts and Skp2 knockdown HeLa cells. Moreover, cyclin D1 expression was suppressed in Skp2 knockdown HeLa cells. These data suggest that Tob1 is a novel target for degradation by the SCF-Skp2 ubiquitin ligase.

ジャーナルCancer Research
出版物ステータス出版済み - 9 1 2006


All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


Hiramatsu, Y., Kitagawa, K., Suzuki, T., Uchida, C., Hattori, T., Kikuchi, H., ... Kitagawa, M. (2006). Degradation of Tob1 mediated by SCFSkp2-dependent ubiquitination. Cancer Research, 66(17), 8477-8483.