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Proteasome-mediated degradation of Rac1-GTP during epithelial cell scattering.

ABSTRACT: Epithelial cells disassemble their adherens junctions and "scatter" during processes such as tumor cell invasion as well as some stages of embryonic development. Control of actin polymerization is a powerful mechanism for regulating the strength of cell-cell adhesion. In this regard, studies have shown that sustained activation of Rac1, a well-known regulator of actin dynamics, results in the accumulation of polymerized actin at cell-cell contacts in epithelia and an increase in E-cadherin-mediated adhesion. Here we show that active Rac1 is ubiquitinated and subject to proteasome-mediated degradation during the early stages of epithelial cell scattering. These findings delineate a mechanism for the down-regulation of Rac1 in the disassembly of epithelial cell-cell contacts and support the emerging theme that UPS-mediated degradation of the Rho family GTPases may serve as an efficient mechanism for GTPase deactivation in the sustained presence of Dbl-exchange factors.

SUBMITTER: Lynch EA

PROVIDER: S-EPMC1446081 | biostudies-other | 2006 May

REPOSITORIES: biostudies-other

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Proteasome-mediated degradation of Rac1-GTP during epithelial cell scattering.

Lynch Emma A EA Stall Jennifer J Schmidt Gudila G Chavrier Philippe P D'Souza-Schorey Crislyn C

Molecular biology of the cell 20060215 5

Epithelial cells disassemble their adherens junctions and "scatter" during processes such as tumor cell invasion as well as some stages of embryonic development. Control of actin polymerization is a powerful mechanism for regulating the strength of cell-cell adhesion. In this regard, studies have shown that sustained activation of Rac1, a well-known regulator of actin dynamics, results in the accumulation of polymerized actin at cell-cell contacts in epithelia and an increase in E-cadherin-media ...[more]

PMID: 16481404

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