Role of a ribosome-associated E3 ubiquitin ligase in protein quality control.
Role of a ribosome-associated E3 ubiquitin ligase in protein quality control.
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mRNA lacking stop codons (“nonstop mRNA”) can arise from errors in gene expression, and encode aberrant proteins whose accumulation could be deleterious to cellular function. In bacteria, such “nonstop proteins” become co-translationally tagged with a peptide encoded by tmRNA/ssrA, which signals their degradation by energy-dependent proteases. How eukaryotic cells eliminate nonstop proteins has remained unknown. Here we show that the S. cerevisiae Ltn1 RING domain-type E3 ubiquitin ligase acts in the quality control of nonstop proteins, in a process that is mechanistically distinct but conceptually analogous to the one carried out by ssrA: Ltn1 is predominantly associated with ribosomes, and marks nascent nonstop proteins with ubiquitin to signal their proteasomal degradation. Ltn1-mediated ubiquitylation of nonstop proteins appears to be triggered by their stalling in ribosomes upon translation through the poly(A) tail. The biological relevance of this process is underscored by the finding that loss of Ltn1 function conferred sensitivity to stress caused by increased nonstop protein production. We speculate that defective protein quality control may underlie the neurodegenerative phenotype that results from mutation of the mouse Ltn1 homolog, Listerin.
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影响因子：
16.8
作者：
通讯作者：
--
影响因子：
3.7
作者：
Li W;Bengtson MH;Ulbrich A;Matsuda A;Reddy VA;Orth A;Chanda SK;Batalov S;Joazeiro CA
通讯作者：
Joazeiro CA
DOI：
10.1073/pnas.0812819106
发表时间：
2009-02-17
影响因子：
11.1
作者：
Chu, Jessie;Hong, Nancy A.;Kay, Steve A.
通讯作者：
Kay, Steve A.
影响因子：
4.8
作者：
Dimitrova, Lyudmila N.;Kuroha, Kazushige;Inada, Toshifumi
通讯作者：
Inada, Toshifumi
影响因子：
11.4
作者：
Inada, T;Aiba, H
通讯作者：
Aiba, H