Open Access
Subscription or Fee Access
15 PERK and Translational Control by Stress in the Endoplasmic Reticulum
Abstract
TRANSLATIONAL CONTROL IN THE UNFOLDED PROTEIN RESPONSE: HISTORICAL BACKGROUND
Protein folding is the last step in gene expression. The information required for folding is encoded in the genome and is an intrinsic property of the translated polypeptide. However, in the crowded environment of the cell this process is rarely spontaneous; specific chaperone systems have evolved to assist in folding (Anfinsen 1973). The work they perform is energetically very costly and their function is dependent on the environment in the different cellular compartments. Consequently, physical, biochemical, and genetic perturbations can unfavorably affect the process of folding, resulting in the accumulation of malfolded proteins. The biological consequence of production and accumulation of malfolded proteins is not completely understood; however, it is a highly disadvantageous situation for the cell. For this reason, cells from all phyla have evolved means of dealing with the stress imposed by malfolded and abnormal proteins. One of the best-characterized responses consists of a global attenuation in translation initiation rates. This response is thought to be adaptive insomuch as it reduces the burden on the folding machinery during times of excessive demand. In mammalian cells it appears that this conceptually simple feedback loop is compartmentalized and utilizes sensing and effecting modalities that have considerable specificity to both compartment and challenge. Other chapters in this book deal with translational control in the context of heat shock (Chapter 17), viral infection (Chapter 9) and nutrient deprivation (Chapter 5). This chapter focuses on a signaling pathway that operates in the endoplasmic reticulum...
Protein folding is the last step in gene expression. The information required for folding is encoded in the genome and is an intrinsic property of the translated polypeptide. However, in the crowded environment of the cell this process is rarely spontaneous; specific chaperone systems have evolved to assist in folding (Anfinsen 1973). The work they perform is energetically very costly and their function is dependent on the environment in the different cellular compartments. Consequently, physical, biochemical, and genetic perturbations can unfavorably affect the process of folding, resulting in the accumulation of malfolded proteins. The biological consequence of production and accumulation of malfolded proteins is not completely understood; however, it is a highly disadvantageous situation for the cell. For this reason, cells from all phyla have evolved means of dealing with the stress imposed by malfolded and abnormal proteins. One of the best-characterized responses consists of a global attenuation in translation initiation rates. This response is thought to be adaptive insomuch as it reduces the burden on the folding machinery during times of excessive demand. In mammalian cells it appears that this conceptually simple feedback loop is compartmentalized and utilizes sensing and effecting modalities that have considerable specificity to both compartment and challenge. Other chapters in this book deal with translational control in the context of heat shock (Chapter 17), viral infection (Chapter 9) and nutrient deprivation (Chapter 5). This chapter focuses on a signaling pathway that operates in the endoplasmic reticulum...
DOI: http://dx.doi.org/10.1101/0.547-560