GSK-3β in DNA repair, apoptosis, and resistance of chemotherapy, radiotherapy of cancer

Abstract

Glycogen synthase kinase-3β (GSK-3β) is an evolutionarily conserved serine/threonine kinase, functioning in numerous cellular processes including cell proliferation, DNA repair, cell cycle, signaling and metabolic pathways. GSK-3β is implicated in different diseases including inflammation, neurodegenerative disease, diabetes and cancers. GSK-3β is involved in biological processes of tumorigenesis, therefore, it is rational that GSK-3β inhibitors were employed to target malignant tumors. The effects of GSK-3β inhibitors in combination of radiation and chemotherapeutic drugs have been reported in various types of cancers, suggesting GSK-3β would play important roles in cancer treatments. GSK-3β is involved in multiple signal pathway including Wnt/β-catenin, PI3K/PTEN/AKT and Notch. GSK-3β also functions in DNA repair through phosphorylation of DNA repair factors and affecting their binding to chromatin. This review focuses on the molecular mechanism of GSK-3β in DNA repair, special in base excision repair and double-strands break repair, the roles of GSK-3β in inhibition of apoptosis through activation of NF-κB, and the effects of GSK-3β inhibitors on radio- and chemosensitization of various types of cancers. This article is part of a Special Issue entitled: GSK-3 and related kinases in cancer, neurological and other disorders edited by James McCubrey, Agnieszka Gizak and Dariusz Rakus.