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Biochimie. 2014 Apr;99:19-27. doi: 10.1016/j.biochi.2013.11.003. Epub 2013 Nov 14.

A crosstalk between p21 and UPR-induced transcription factor C/EBP homologous protein (CHOP) linked to type 2 diabetes.

Author information

1
Department of Biological Chemistry, University of Athens Medical School, 11527 Athens, Greece.
2
Department of Biological Chemistry, University of Athens Medical School, 11527 Athens, Greece. Electronic address: hkiaris@med.uoa.gr.

Abstract

Type 2 diabetes (T2D) is a disease that is characterized by raised levels of glucose in the blood combined with insulin resistance and relative insulin deficiency. The pathogenesis of type 2 diabetes is associated with the induction of the unfolded protein response (UPR). While UPR aims to restore tissue homeostasis following stress of the endoplasmic reticulum (ER), prolonged ER stress triggers apoptosis at least in part through the unfolded protein response (UPR)-activated transcription factor C/EBP (CCAAT/enhancer binding protein) homologous protein (CHOP). CHOP has elevated as a critical mediator connecting accumulation and aggregation of unfolded proteins in the ER and oxidative stress and also contributes to the induction of apoptosis in β-cell (beta-cell) - cells under conditions of increased insulin demand. p21 is a cell cycle regulator that is implicated in the regulation of the UPR by various mechanisms involving inhibition of apoptosis and facilitation of the regeneration capacity of the β cells. In this review we summarize the role of ER stress in the pathogenesis of type 2 diabetes which is associated with the induction of the unfolded protein response (UPR). We also review recent evidence associating p21 activity with β cell health and regenerative capacity by mechanisms that may interfere with the effects of p21 in the UPR or operate independently of ER stress. Most likely understanding the molecular details of the pathogenesis of type 2 diabetes will be beneficial for the management of the disease.

KEYWORDS:

Apoptosis; CHOP; Diabetes; ER-stress; UPR; p21

PMID:
24239558
DOI:
10.1016/j.biochi.2013.11.003
[Indexed for MEDLINE]

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