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2011

Glycogen synthase kinase 3 and cancer - an overview

Author:Avani P. Shah

Abstract:
Defective apoptosis (programmed cell death) represents a major causative factor in the development and progression of cancer. Glycogen Synthase Kinase-3 (GSK-3) has the perplexing capacity to either increase or decrease the apoptotic threshold. These apparently paradoxical effects now are known to be due to GSK-3 which oppositely regulating the two major apoptotic signaling pathways. GSK-3 promotes cell death caused by the mitochondrial intrinsic apoptotic pathway, but inhibits the death receptor-mediated extrinsic apoptotic signaling pathway. Consequently, inhibitors of GSK-3 provide protection from intrinsic apoptosis signaling but potentiate extrinsic apoptosis signaling. So, ability of GSK-3 to oppositely influence two types of apoptotic signaling have thrown a light on important regulatory mechanisms in apoptosis and henceforth designing the rational use of GSK-3 inhibitors for therapeutic interventions in cancer.