title: Targeting unfolded protein response in cancer and diabetes.
abstract: The maturation of secretory and membrane proteins in the endoplasmic reticulum (ER) is tightly regulated by the unfolded protein response (UPR), a signal transduction pathway maintaining ER protein folding homeostasis. However, certain ER states are incompatible with cell survival and therefore the UPR may choose to eliminate severely disrupted cells by apoptosis. This is accomplished primarily through the activation of the transcription factor CCAAT-enhancer-binding protein homologous protein (CHOP). In the April 2015 issue of Endocrine-Related Cancer, researchers from the universities of South Carolina and Athens (Greece) suggested a novel mechanism of CHOP-mediated apoptosis connected with the suppression of a prominent cell cycle regulator with anti-apoptotic activity, p21. These findings and suggested clinical applications, such as potentiation of cancer chemotherapy and a novel therapeutic approach for type 2 diabetes, are discussed in the context of UPR.
authors: Section of PharmacogeneticsDepartment of Physiology and Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden souren.mkrtchian@ki.se.
authors: Souren
authors: S
authors: Mkrtchian
mesh_terms: D000818:Animals; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D005260:Female; D006801:Humans; D051742:Transcription Factor CHOP / Q000378:metabolism*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D051742:Transcription Factor CHOP
keywords: chemotherapy; intracellular signaling; islet cells; oncology