Journal
SCIENCE
Volume 302, Issue 5651, Pages 1775-1779Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1090772
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Funding
- NICHD NIH HHS [R01 HD032429-06, R01 HD032429-07, HD32429, R01 HD032429] Funding Source: Medline
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The Rho family of small guanosine triphosphatases regulates actin cytoskeleton dynamics that underlie cellular functions such as cell shape changes, migration, and polarity. We found that Smurf1, a HECT domain E3 ubiquitin ligase, regulated cell polarity and protrusive activity and was required to maintain the transformed morphology and motility of a tumor cell. Atypical protein kinase C zeta (PKCzeta), an effector of the Cdc42/Rac1-PAR6 polarity complex, recruited Smurf1 to cellular protrusions, where it controlled the local level of RhoA. Smurf1 thus links the polarity complex to degradation of RhoA in lamellipodia and filopodia to prevent RhoA signaling during dynamic membrane movements.
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