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Updated: Aug 19, 2026

Comparing the Affinity of GTPase-binding Proteins using Competition Assays
Published on: October 8, 2015
The FWD1/beta-TrCP-mediated degradation pathway establishes a 'turning off switch' of a Cdc42 guanine nucleotide
Makio Hayakawa1, Hideo Kitagawa, Keiji Miyazawa
1School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. hayakawa@ps.toyaku.ac.jp
Abstract:
FWD1/beta-TrCP is the F-box protein that functions as the receptor subunit of the SCF(FWD1/beta-TrCP) ubiquitin ligase and has been shown to be responsible for the degradation of important signaling molecules such as IkappaBs and beta-catenin. Protein substrates of FWD1/beta-TrCP contain a consensus DSGPsiXS motif (where Psi represents a hydrophobic residue and X represents any amino acid). Recognition by FWD1/beta-TrCP requires phosphorylation of the conserved serines in that motif. Here we show that FGD1, a Cdc42 guanine nucleotide exchange factor (GEF), is a novel target of the SCF(FWD1/beta-TrCP) ubiquitin ligase. A mutant FGD1 protein, FGD1(SA), in which both of the critical serine residues in the DSGPsiXS motif have been replaced by alanines, does not interact with FWD1/beta-TrCP and exhibits increased stability. Morphological changes induced by wild-type FGD1 (FGD1(WT)) are reduced by the co-expression of SCF(FWD1/beta-TrCP) whereas those induced by FGD1(SA) are not affected. FGD1(SA)-expressing cells show a higher level of cell motility than FGD1(WT)-expressing cells. We present a novel 'turning off' mechanism for the inactivation of FGD1, an upstream regulator for Cdc42.
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