Figure 17-28. The unfolded-protein response.

Figure 17-28The unfolded-protein response

IRE1 is a transmembrane protein in the inner nuclear membrane, a membrane that is continuous with the ER membrane. This multifunctional protein (green) has a binding site for unfolded proteins (blue) on its luminal surface; its nuclear-facing domain contains a protein kinase of unknown function and a specific RNA endonuclease. Binding of unfolded proteins in the ER lumen dimerizes the receptor and somehow activates the endonuclease, which cleaves the unspliced mRNA precursor encoding the transcription factor HAC1. The two exons of HAC1 mRNA then are linked together by tRNA ligase, which usually splices tRNA precursors, forming a functional HAC1 mRNA. Following its synthesis in the cytosol, HAC1 protein moves back into the nucleus and activates transcription of genes encoding several chaperones and other proteins that assist in folding unfolded proteins in the ER lumen. [See C. Sidrauski and P. Walter, 1997, Cell 90:1031.]

From: Section 17.6, Post-Translational Modifications and Quality Control in the Rough ER

Cover of Molecular Cell Biology
Molecular Cell Biology. 4th edition.
Lodish H, Berk A, Zipursky SL, et al.
New York: W. H. Freeman; 2000.
Copyright © 2000, W. H. Freeman and Company.

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