Trusina A, Papa FR*, Tang C*, Benefits of translation attenuation in the unfolded protein response: A modeling approach, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 105, 20280, 2008.

Abstract Increased levels of unfolded proteins in the endoplasmic reticulum(ER) of all eukaryotes trigger the unfolded protein response (UPR).Lower eukaryotes solely use an ancient UPR mechanism, whereby they up-regulate ER-resident chaperones and other enzymatic activities to augment protein folding and enhance degradation of misfolded proteins. Metazoans have evolved an additional mechanism through which they attenuate translation of secretory pathway proteins by activating the ER protein kinase PERK. In mammalian professional secretory cells such as insulin-producing pancreatic -cells, PERK is highly abundant and crucial for proper functioning of the secretory pathway. Through a modeling approach, wepropose explanations for why a translation attenuation (TA) mechanism may be critical fo......