Rationalizing translation attenuation in the network architecture of the unfolded protein response.

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 beta-cells, PERK is highly abundant and crucial for proper functioning of the secretory pathway. Through a modeling approach, we propose explanations for why a translation attenuation (TA) mechanism may be critical for

SUBMITTER: Trusina A 

PROVIDER: S-EPMC2603256 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature