Degradation of Tob1 mediated by SCFSkp2-dependent ubiquitination.
Hiramatsu Y,
Kitagawa K,
Suzuki T,
Uchida C,
Hattori T,
Kikuchi H,
Oda T,
Hatakeyama S,
Nakayama KI,
Yamamoto T,
Konno H,
Kitagawa M.
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
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.
PMID: 16951159 [PubMed - indexed for MEDLINE]