The Cdc42p effector Gic2p is targeted for ubiquitin-dependent degradation by the SCFGrr1 complex

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Abstract
Cdc42p, a Rho‐related GTP‐binding protein, regulates cytoskeletal polarization and rearrangements in eukaryotic cells. In yeast, Gic1p and Gic2p are effectors of Cdc42p involved in actin polarization at bud emergence. Gic2p is expressed in a cell cycle‐dependent manner and rapidly disappears shortly after bud emergence concomitant with the activation of the G1 cyclin‐dependent kinase Cdc28p–Clnp. Here we have shown that the rapid disappearance of Gic2p results from ubiquitin‐dependent proteolysis. Biochemical and genetic evidence demonstrates that degradation of Gic2p required the Skp1–cullin–F‐box protein complex (SCF) components Cdc34p, Cdc53p, Skp1p and Grr1p, but not Cdc4p. Phosphorylation of several C‐terminal sites of Gic2p served as part of the recognition signal for ubiquitination. In addition, binding of Gic2p to Cdc42p was a prerequisite for degradation, suggesting that specifically the active form of Gic2p is targeted for destruction. Finally, our data indicate that degradation of Gic2p may be part of a mechanism which restricts cytoskeletal polarization in the G1 phase of the cell cycle.