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Biology Articles » Biochemistry » Signaling the Unfolded Protein Response from the Endoplasmic Reticulum

Abstract
- Signaling the Unfolded Protein Response from the Endoplasmic Reticulum

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Signaling the Unfolded Protein Response from the Endoplasmic Reticulum*

Kezhong Zhang{ddagger} and Randal J. Kaufman{ddagger}§

From the {ddagger}Department of Biological Chemistry and §Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109

INTRODUCTION  
Eukaryotic cells have a membranous labyrinth network called the endoplasmic reticulum (ER)1 that extends through the cytoplasm of the cell and is contiguous with the nuclear envelope. Proteins must be correctly folded and assembled in the ER prior to transit to intracellular organelles and the cell surface. As a processing plant for protein folding and posttranslational modification, the ER is exquisitely sensitive to alterations in homeostasis. A number of cellular stress conditions, such as perturbation in calcium homeostasis or redox status, elevated secretory protein synthesis, expression of misfolded proteins, sugar/glucose deprivation, altered glycosylation, and overloading of cholesterol can interfere with oxidative protein folding and subsequently lead to accumulation of unfolded or misfolded proteins in the ER lumen, which constitutes a fundamental threat to the cells. The ER has evolved highly specific signaling pathways to alter transcriptional and translational programs to cope with the accumulation of unfolded or misfolded proteins in the ER lumen. This adaptive response, which couples the ER protein folding load with the ER protein folding capacity, is termed the unfolded protein response (UPR) (14). Over the past 10 years, significant progress has been made in understanding the mechanisms and roles of UPR signaling. Here we discuss the basic components of the UPR pathways, the physiological roles of the UPR signaling, and the future direction of the field.

Source: J. Biol. Chem., Vol. 279, Issue 25, 25935-25938, June 18, 2004


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