Phosphorylation-dependent regulation of cytosolic localization and oncogenic function of Skp2 by Akt/PKB.

ABSTRACT: Skp2 is an F-box protein that forms the SCF complex with Skp1 and Cullin-1 to constitute an E3 ligase for ubiquitylation. Ubiquitylation and degradation of the p27 are critical for Skp2-mediated entry to the cell cycle, and overexpression and cytosolic accumulation of Skp2 have been clearly associated with tumorigenesis, although the functional significance of the latter is still unknown. Here we show that Akt/protein kinase B (PKB) interacts with and directly phosphorylates Skp2. We find that Skp2 phosphorylation by Akt triggers SCF complex formation and E3 ligase activity. A phosphorylation-defective Skp2 mutant is drastically impaired in its ability to promote cell proliferation and tumorigenesis. Furthermore, we show that Akt-mediated phosphorylation triggers 14-3-3beta-dependent Skp2

SUBMITTER: Lin HK 

PROVIDER: S-EPMC2830812 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature