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Physiological Reviews, Vol. 79, No. 3, July 1999, pp. 683-701
Copyright ©1999 by the American Physiological Society
Department of Experimental Anesthesiology, University Hospital Freiburg, Freiburg, Germany
Pahl, Heike L.
Signal Transduction From the Endoplasmic Reticulum to the
Cell Nucleus. Physiol. Rev. 79: 683-701, 1999.
The endoplasmic reticulum (ER) serves several important
functions. Cholesterol, an essential component of cellular membranes, is synthesized on the ER surface. Inside the organelle, proteins destined for secretion or transport to the cell surface are folded and
become glycosylated. Because these processes are essential for cell
viability, a disturbance in ER function presents significant stress to
the cell. In response to ER stress, three distinct signal transduction
pathways can be activated. Two of these, the unfolded protein response
and the ER-overload response, respond to disturbances in protein
processing. The third, the sterol regulatory cascade, is activated by
depletion of cholesterol. This review summarizes the recent advances in
our understanding of these ER-nuclear signal transduction pathways.
In addition, it points to novel regulatory mechanisms discovered in
these pathways, which may be widely used in other systems.
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