PT  - JOURNAL ARTICLE
AU  - Hiramatsu, Yoshihiro
AU  - Kitagawa, Kyoko
AU  - Suzuki, Toru
AU  - Uchida, Chiharu
AU  - Hattori, Takayuki
AU  - Kikuchi, Hirotoshi
AU  - Oda, Toshiaki
AU  - Hatakeyama, Shigetsugu
AU  - Nakayama, Keiichi I.
AU  - Yamamoto, Tadashi
AU  - Konno, Hiroyuki
AU  - Kitagawa, Masatoshi
TI  - Degradation of Tob1 Mediated by SCF<sup>Skp2</sup>-Dependent Ubiquitination
AID  - 10.1158/0008-5472.CAN-06-1603
DP  - 2006 Sep 01
TA  - Cancer Research
PG  - 8477--8483
VI  - 66
IP  - 17
4099  - http://cancerres.aacrjournals.org/content/66/17/8477.short
4100  - http://cancerres.aacrjournals.org/content/66/17/8477.full
SO  - Cancer Res2006 Sep 01; 66
AB  - Tob1, a member of the Tob/BTG family, is involved in the control of G1-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. (Cancer Res 2006; 66(17): 8477-83) ©2006 American Association for Cancer Research.