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

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)8477-8483
Number of pages7
JournalCancer Research
Volume66
Issue number17
DOIs
Publication statusPublished - Sep 1 2006

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Degradation of Tob1 mediated by SCF<sup>Skp2</sup>-dependent ubiquitination'. Together they form a unique fingerprint.

  • Cite this

    Hiramatsu, Y., Kitagawa, K., Suzuki, T., Uchida, C., Hattori, T., Kikuchi, H., Oda, T., Hatakeyama, S., Nakayama, K. I., Yamamoto, T., Konno, H., & Kitagawa, M. (2006). Degradation of Tob1 mediated by SCFSkp2-dependent ubiquitination. Cancer Research, 66(17), 8477-8483. https://doi.org/10.1158/0008-5472.CAN-06-1603