Regulatory mechanism of Cdc42p turnover, and its impact on fMAPK pathway activity. Cdc42p is known to be activated by GEFs and inactivated by GAPs. Here, we show that GTP-bound Cdc42p is ubiquitinated and turned over by a mechanism involving HSP40 (Ydj1p), HSP70 (Ssa1p), and the NEDD4 E3 ubiquitin ligase, Rsp5p. In the model, poly-ubiquitin conjugates of Cdc42p are degraded in the proteasome. Turnover of Cdc42p attenuates fMAPK pathway signaling (green block arrow). By comparison, the Smg GDS-type protein Bem4p stabilizes Cdc42p to promote fMAPK pathway activity. The Cdc42p effectors Bni1p, Gic1p, and Gic2p regulate fMAPK-dependent polarity establishment, and the bud-site selection protein Rsr1p may focus polarization at bud sites (Focus). Block green arrow (Gated) indicates that the mating pathway is not sensitive to Cdc42p levels, because the MAPK Fus3p is catalytically locked when cells are not mating. Cdc42p may be ubiquitinated in other contexts besides those described here. Created with BioRender.com.