Volume 71 Number 5 October 2004	back to contents

Address all correspondence to Linda M. Hendershot, M.D., Department of Genetics and Tumor Cell Biology, St. Jude Children’s Research Hospital, 332 N. Lauderdale, Memphis, TN 38105; E-mail: linda.hendershot@stjude.org

Adapted from a Dean’s Lecture presentation at Mount Sinai School of Medicine, New York, NY on March 19, 2003 and updated as of March 2004.

ABSTRACT
The endoplasmic reticulum (ER) is a command center of the cell that is second only to the nucleus in terms of the breadth of its influence on other organelles and activities. It is a major site of protein synthesis, contains the cellular calcium stores that are an essential component of many signaling pathways, and is the proximal site of a signal transduction cascade that responds to cellular stress conditions and serves to maintain homeostasis of the cell. All eucaryotic cells possess an ER, which can comprise nearly 50% of the membranes of a cell. Its functions can be divided into those that occur on the cytosolic side of the membrane (where protein translation and signal transduction cascades occur) and the luminal space (where most other ER functions take place). Our studies during the past several years have revealed that the ER molecular chaperone BiP is a master regulator of ER function. It is responsible for maintaining the permeability barrier of the ER during protein translocation, directing protein folding and assembly, targeting misfolded proteins for retrograde translocation so they can be degraded by the proteasome, contributing to ER calcium stores, and sensing conditions of stress in this organelle, to activate the mammalian unfolded protein response.

KEY WORDS
ER chaperones, BiP, secretory pathway, ER stress, unfolded protein response.

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