Regulation of Glycogen Synthase Kinase 3β Functions by Modification of the Small Ubiquitin-Like Modifier

Modification of the Small Ubiquitin-like Modifier (SUMO) (SUMOylation) appears to regulate diverse cellular processes, including nuclear transport, signal transduction, apoptosis, autophagy, cell cycle control, ubiquitin-dependent degradation and gene transcription. Glycogen synthase kinase 3β (GSK 3β) is a serine/threonine kinase that is thought to contribute to a variety of biological events, including embryonic development, metabolism, tumorigenesis, and cell death. GSK 3β is a constitutively active kinase that regulates many intracellular signaling pathways by phosphorylating substrates such as β-catenin. We noticed that the putative SUMOylation sites are localized on K(292 )residueof (291)FKFPQ(295) in GSK 3β based on analysis of the SUMOylation consensus sequence. In this report, we showed that the SUMOylation of GSK 3β occurs on its K(292) residue, and this modification promotes its nuclear localization in COS-1. Additionally, our data showed that the GSK 3β SUMO mutant (K292R) decreased its kinase activity and protein stability, affecting cell death. Therefore, our observations at first time suggested that SUMOylation on the K(292) residue of GSK 3β might be a GSK 3β regulation mechanism for its kinase activation, subcellular localization, protein stability, and cell apoptosis.