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Polylysine is a Proteostasis Network-Engaging Structural Determinant
[Image: see text] C-terminal polylysine (PL) can be synthesized from the polyadenine tail of prematurely cleaved mRNAs or when a read-though of a stop codon happens. Due to the highly positive charge, PL stalls in the electrostatically negative ribosomal exit channel. The stalled polypeptide recruit...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983878/ https://www.ncbi.nlm.nih.gov/pubmed/29634277 http://dx.doi.org/10.1021/acs.jproteome.8b00108 |
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author | Lang, Wei-Han Calloni, Giulia Vabulas, R. Martin |
author_facet | Lang, Wei-Han Calloni, Giulia Vabulas, R. Martin |
author_sort | Lang, Wei-Han |
collection | PubMed |
description | [Image: see text] C-terminal polylysine (PL) can be synthesized from the polyadenine tail of prematurely cleaved mRNAs or when a read-though of a stop codon happens. Due to the highly positive charge, PL stalls in the electrostatically negative ribosomal exit channel. The stalled polypeptide recruits the Ribosome-associated quality control (RQC) complex which processes and extracts the nascent chain. Dysfunction of the RQC leads to the accumulation of PL-tagged proteins, induction of a stress response, and cellular toxicity. Not much is known about the PL-specific aspect of protein quality control. Using quantitative mass spectrometry, we uncovered the post-ribosomal PL-processing machinery in human cytosol. It encompasses key cytosolic complexes of the proteostasis network, such as chaperonin TCP-1 ring complexes (TRiC) and half-capped 19S-20S proteasomes. Furthermore, we found that the nuclear transport machinery associates with PL, which suggests a novel mechanism by which faulty proteins can be compartmentalized in the cell. The enhanced nuclear import of a PL-tagged polypeptide confirmed this implication, which leads to questions regarding the biological rationale behind it. |
format | Online Article Text |
id | pubmed-5983878 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-59838782018-06-04 Polylysine is a Proteostasis Network-Engaging Structural Determinant Lang, Wei-Han Calloni, Giulia Vabulas, R. Martin J Proteome Res [Image: see text] C-terminal polylysine (PL) can be synthesized from the polyadenine tail of prematurely cleaved mRNAs or when a read-though of a stop codon happens. Due to the highly positive charge, PL stalls in the electrostatically negative ribosomal exit channel. The stalled polypeptide recruits the Ribosome-associated quality control (RQC) complex which processes and extracts the nascent chain. Dysfunction of the RQC leads to the accumulation of PL-tagged proteins, induction of a stress response, and cellular toxicity. Not much is known about the PL-specific aspect of protein quality control. Using quantitative mass spectrometry, we uncovered the post-ribosomal PL-processing machinery in human cytosol. It encompasses key cytosolic complexes of the proteostasis network, such as chaperonin TCP-1 ring complexes (TRiC) and half-capped 19S-20S proteasomes. Furthermore, we found that the nuclear transport machinery associates with PL, which suggests a novel mechanism by which faulty proteins can be compartmentalized in the cell. The enhanced nuclear import of a PL-tagged polypeptide confirmed this implication, which leads to questions regarding the biological rationale behind it. American Chemical Society 2018-04-10 2018-05-04 /pmc/articles/PMC5983878/ /pubmed/29634277 http://dx.doi.org/10.1021/acs.jproteome.8b00108 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Lang, Wei-Han Calloni, Giulia Vabulas, R. Martin Polylysine is a Proteostasis Network-Engaging Structural Determinant |
title | Polylysine is a Proteostasis Network-Engaging Structural
Determinant |
title_full | Polylysine is a Proteostasis Network-Engaging Structural
Determinant |
title_fullStr | Polylysine is a Proteostasis Network-Engaging Structural
Determinant |
title_full_unstemmed | Polylysine is a Proteostasis Network-Engaging Structural
Determinant |
title_short | Polylysine is a Proteostasis Network-Engaging Structural
Determinant |
title_sort | polylysine is a proteostasis network-engaging structural
determinant |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983878/ https://www.ncbi.nlm.nih.gov/pubmed/29634277 http://dx.doi.org/10.1021/acs.jproteome.8b00108 |
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