| Title: | Chaperone-Dependent Degradation of Cdc42 Promotes Cell Polarity and Shields the Protein from Aggregation |
| Author(s): | Gonzalez B; Aldea M; Cullen PJ; |
| Address: | "Department of Biological Sciences, State University of New York at Buffalo, New York, USA. Molecular Biology Institute of Barcelona (IBMB), CSIC, Barcelona, Spain" |
| DOI: | 10.1080/10985549.2023.2198171 |
| ISSN/ISBN: | 1098-5549 (Electronic) 0270-7306 (Print) 0270-7306 (Linking) |
| Abstract: | "Rho GTPases are global regulators of cell polarity and signaling. By exploring the turnover regulation of the yeast Rho GTPase Cdc42p, we identified new regulatory features surrounding the stability of the protein. We specifically show that Cdc42p is degraded at 37 degrees C by chaperones through lysine residues located in the C-terminus of the protein. Cdc42p turnover at 37 degrees C occurred by the 26S proteasome in an ESCRT-dependent manner in the lysosome/vacuole. By analyzing versions of Cdc42p that were defective for turnover, we show that turnover at 37 degrees C promoted cell polarity but was defective for sensitivity to mating pheromone, presumably mediated through a Cdc42p-dependent MAP kinase pathway. We also identified one residue (K16) in the P-loop of the protein that was critical for Cdc42p stability. Accumulation of Cdc42p(K16R) in some contexts led to the formation of protein aggregates, which were enriched in aging mother cells and cells undergoing proteostatic stress. Our study uncovers new aspects of protein turnover regulation of a Rho-type GTPase that may extend to other systems. Moreover, residues identified here that mediate Cdc42p turnover correlate with several human diseases, which may suggest that turnover regulation of Cdc42p is important to aspects of human health" |
| Keywords: | "Humans *cdc42 GTP-Binding Protein, Saccharomyces cerevisiae/metabolism *Cell Polarity/physiology Saccharomyces cerevisiae/metabolism *Saccharomyces cerevisiae Proteins/genetics/metabolism Signal Transduction Escrt aging protein aggregation protein traffic;" |
| Notes: | "MedlineGonzalez, Beatriz Aldea, Marti Cullen, Paul J eng Research Support, N.I.H., Extramural 2023/04/28 Mol Cell Biol. 2023; 43(5):200-222. doi: 10.1080/10985549.2023.2198171. Epub 2023 Apr 28" |
