Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

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


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).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882