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Sci. STKE, 5 June 2001
Vol. 2001, Issue 85, p. tw6
[DOI: 10.1126/stke.2001.85.tw6]

EDITORS' CHOICE

Cell Biology Destroying β-Catenin

Regulating the cytosolic concentration of the protein β-catenin is an important cell proliferation control mechanism. The cytoplasmic concentration of β-catenin remains low through an interaction with a protein complex consisting of adenomatous polyposis coli (APC), Axin, protein phosphatase 2A, and glycogen synthase kinase 3β (GSK3β). Upon phosphorylation by GSK3β, β-catenin associates with a ubiquitin ligase (E3) complex, resulting in its ubiquitination and proteolysis. Activation of Wnt signaling inactivates GSK3, allowing β-catenin to accumulate in the cytoplasm and eventually to translocate to the nucleus so as to affect gene expression. Two groups report that a phosphorylation-independent mechanism can lead to the destruction of β-catenin. Matsuzawa and Reed show that a mammalian protein called Siah-1 lies at the hub of another pathway that destroys β-catenin in response to DNA damaging agents and the activation of the tumor suppressor protein p53. Siah-1 is known to interact with E2 ubiquitin-conjugating enzymes. In a protein interaction screen, a Siah-1 interacting protein (SIP) was discovered. SIP was found to bind to a protein called Ebi, which not only binds to β-catenin, but targets it to an E3 ubiquitinase complex and hence, leads to the proteolysis of β-catenin. Liu et al. report that Siah-1 also interacts with APC, which is required for Siah-1-dependent degradation of β-catenin. This alternate β-catenin destruction pathway may link p53 to cell-cycle arrest.

S. Matsuzawa, J.C. Reed, Siah-1, SIP, and Ebi collaborate in a novel pathway for β-catenin degradation linked to p53 responses. Mol. Cell 7, 915-926 (2001). [Online Journal]

J. Liu, J. Stevens, C. A. Rote, H. J. Yost, Y. Hu, K. L. Neufeld, R. L. White, N. Matsunami, Siah-1 mediates a novel β-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein. Mol. Cell 7, 927-936 (2001). [Online Journal]

Citation: Destroying β-Catenin. Sci. STKE 2001, tw6 (2001).


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