Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses

Destruction of beta -catenin is regulated through phosphorylation-dependent interactions with the F box protein beta -TrCP. A novel pathway for beta - catenin degradation was discovered involving mammalian homologs of Drosophi la Sina (Siah), which bind ubiquitin-conjugating enzymes, and Ebi, an F box protein that binds beta -catenin independent of the phosphorylation sites recognized by beta -TrCP. A series of protein interactions were identified in which Siah is physically linked to Ebi by association with a novel Sgt1 homolog SIP that binds Skp1, a central component of Skp1 -Cullin-F box comp lexes. Expression of Siah is induced by p53, revealing a way of linking gen otoxic injury to destruction of beta -catenin, thus reducing activity of Tc f/LEF transcription factors and contributing to cell cycle arrest.