Regulation of cell polarity and protrusion formation by targeting RhoA for degradation.
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.
PubMed ID: 14657501
Article link: Science.
Genes referenced: cdc42 pard6b prkci prkcz rac1 rho rhoa rhoa.2 smurf1
Antibodies referenced: Smurf1 Ab1