Related Experiment Video
Updated: Apr 21, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
Published on: March 9, 2012
PLK1 and β-TrCP-dependent ubiquitination and degradation of Rap1GAP controls cell proliferation
Dejie Wang1, Pingzhao Zhang2, Kun Gao3
1State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, P.R. China; Department of Gastroenterology, Jiangxi Institute of Gastroenterology & Hepatology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, P. R. China.
Abstract:
Rap1GAP is a GTPase-activating protein (GAP) that specifically stimulates the GTP hydrolysis of Rap1 GTPase. Although Rap1GAP is recognized as a tumor suppressor gene and downregulated in various cancers, little is known regarding the regulation of Rap1GAP ubiquitination and degradation under physiological conditions. Here, we demonstrated that Rap1GAP is ubiquitinated and degraded through proteasome pathway in mitosis. Proteolysis of Rap1GAP requires the PLK1 kinase and β-TrCP ubiquitin ligase complex. We revealed that PLK1 interacts with Rap1GAP in vivo through recognition of an SSP motif within Rap1GAP. PLK1 phosphorylates Ser525 in conserved 524DSGHVS529 degron of Rap1GAP and promotes its interaction with β-TrCP. We also showed that Rap1GAP was a cell cycle regulator and that tight regulation of the Rap1GAP degradation in mitosis is required for cell proliferation.
Related Concept Videos
PI3K/mTOR/AKT Signaling Pathway
Negative Regulator Molecules
Regulated Protein Degradation
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Inhibition of Cdk Activity
MAPK Signaling Cascades

