Regulation of PTEN stability and activity

PTEN protein stability is regulated by ubiquitin ligases, such as NEDD4, WWP2, STUB1 (CHIP), XIAP, MKRN1 and RNF146, which polyubiquitinate PTEN in response to different stimuli and thus target it for proteasome-mediated degradation (Wang et al. 2007, Van Themsche et al. 2009, Maddika et al. 2011, Ahmed et al. 2012, Lee et al. 2015, Li et al. 2015). Several ubiquitin proteases, such as USP13 and OTUD3, can remove polyubiquitin chains from PTEN and rescue it from degradation. TRIM27 (RFP) is an E3 ubiquitin ligase that polyubiquitinates PTEN on multiple lysines in the C2 domain of PTEN using K27 linkage between ubiquitin molecules. TRIM27 mediated ubiquitination inhibits PTEN lipid phosphatase activity, but does not affect PTEN protein localization or stability.

Summary from Reactome (R-HSA-8948751), read 2026-09-23.