Claudio Joazeiro, "Listerin/Ltn1 links Co-translational Protein Quality Control and Neurodegeneration"
Nov 11, 2013 (Mon) | 4:00 PM -4:00 PM
393 Serra Mall, Herrin T-175 : Stanford, CA
Abstract: mRNA lacking stop codons ('non-stop mRNA') can arise from errors in gene expression, and encode aberrant proteins whose accumulation could be deleterious to cellular function. We have recently reported that the S. cerevisiae Ltn1 RING domain protein acts as the E3 ligase responsible for non-stop protein ubiquitination and degradation (Bengtson & Joazeiro 2010. Nature 467:470-3). The Ltn1-mediated process is triggered as ribosomes translating a non-stop mRNA reach the poly(A) tail; the latter encodes polyLys, whose synthesis causes translational elongation to stall. We have found that this in turn acts as a signal for the recruitment of Ltn1. The biological relevance of this process is underscored by the finding that loss of Ltn1 function confers sensitivity to stress caused by increased non-stop protein production. We propose that defective protein quality control may underlie the neurodegenerative phenotype resulting from mutation of the mouse Ltn1 homologue, Listerin. In my talk, I will review these data and present more recent findings and further characterization of the Listerin/Ltn1 pathway.
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