Regulation of Glycogen Synthase Kinase 3β Functions by Modification of the Small Ubiquitin-Like Modifier
Eun Jeoung Lee1, Sung Hee Hyun2, Jaesun Chun3, Sung Hwa Shin1, Kwang Hum Yeon3, Min Kyoung Kwak1, Tae Yoon Park4, Sang Sun Kang*, 1
1 School of Science Education, Chungbuk National University, Gaeshin-dong, Heungdok-gu, Cheongju, Chungbuk, 361-763, Republic of Korea.
2 Department of Pre-medicine, Eulji University School of Medicine, Daejeon 301-832, Republic of Korea
3 Department of Biology Education, Korea National University of Education, Chongwon, Chungbuk 363-791, Republic of Korea
4 Graduate School of Education, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, Republic of Ko-rea
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 K292 residueof 291FKFPQ295 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 K292 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 K292 residue of GSK 3β might be a GSK 3β regulation mechanism for its kinase activation, subcellular localization, protein stability, and cell apoptosis.
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* Address correspondence to these authors at the School of Science Education, Chungbuk National University, Gaeshin-dong, Heungdok-gu, Chongju, Chungbuk, 361-763, Republic of KoreaDepartment of Biology Education, Korea National University of Education, Chongwon, Chungbuk 363-791, Republic of Korea; Tel; +82 43 261 3278; Fax; +82 43 271 0526; E- mail: firstname.lastname@example.org