Cell Biology

Destroying to Rebuild

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Science  01 Mar 2002:
Vol. 295, Issue 5560, pp. 1605
DOI: 10.1126/science.295.5560.1605c

Epithelial cells are glued together by cell adhesion molecules, and the modulation of cell adhesion may be important in regulating differentiation of epithelia during development. E-cadherin is a substrate for tyrosine kinases, and tyrosine phosphorylation is followed by further posttranslational modification, the addition of ubiquitin molecules. Ubiquitination of E-cadherins causes their internalization and increases cell motility. Fujita et al. find that the protein Hakai (which means destruction in Japanese) binds specifically to tyrosine-phosphorylated E-cadherin and acts to stimulate ubiquitination and endocytosis. In cells expressing increased levels of Hakai, cell-cell contacts are disrupted, and internalization of E-cadherin is increased, as is cell motility. These effects of Hakai can be attributed directly to its being a member of the family of E3 ubiquitin ligases, enzymes that catalyze the terminal step in ubiquitination pathways. — SMH

Nature Cell Biol., 10.1038/ncb758.

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