Cdc48/p97 promotes degradation of aberrant nascent polypeptides bound to the ribosome
Ubiquitin-dependent proteolysis can initiate at ribosomes for myriad reasons including misfolding of a nascent chain or stalling of the ribosome during translation of mRNA. Clearance of a stalled complex is required to recycle the ribosome for future use. Here we show that the ubiquitin (Ub) pathway...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2013-01-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/00308 |
| _version_ | 1811200141936295936 |
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| author | Rati Verma Robert S Oania Natalie J Kolawa Raymond J Deshaies |
| author_facet | Rati Verma Robert S Oania Natalie J Kolawa Raymond J Deshaies |
| author_sort | Rati Verma |
| collection | DOAJ |
| description | Ubiquitin-dependent proteolysis can initiate at ribosomes for myriad reasons including misfolding of a nascent chain or stalling of the ribosome during translation of mRNA. Clearance of a stalled complex is required to recycle the ribosome for future use. Here we show that the ubiquitin (Ub) pathway segregase Cdc48/p97 and its adaptors Ufd1-Npl4 participate in ribosome-associated degradation (RAD) by mediating the clearance of ubiquitinated, tRNA-linked nascent peptides from ribosomes. Through characterization of both endogenously-generated and heterologous model substrates for the RAD pathway, we conclude that budding yeast Cdc48 functions downstream of the Ub ligases Ltn1 and Ubr1 to release nascent proteins from the ribosome so that they can be degraded by the proteasome. Defective RAD could contribute to the pathophysiology of human diseases caused by mutations in p97. |
| first_indexed | 2024-04-12T01:58:46Z |
| format | Article |
| id | doaj.art-0e9700d971ba403f9a2606c83465e45d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:58:46Z |
| publishDate | 2013-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-0e9700d971ba403f9a2606c83465e45d2022-12-22T03:52:43ZengeLife Sciences Publications LtdeLife2050-084X2013-01-01210.7554/eLife.00308Cdc48/p97 promotes degradation of aberrant nascent polypeptides bound to the ribosomeRati Verma0Robert S Oania1Natalie J Kolawa2Raymond J Deshaies3Division of Biology, California Institute of Technology, Pasadena, United States; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, United StatesDivision of Biology, California Institute of Technology, Pasadena, United States; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, United StatesDivision of Biology, California Institute of Technology, Pasadena, United StatesDivision of Biology, California Institute of Technology, Pasadena, United States; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, United StatesUbiquitin-dependent proteolysis can initiate at ribosomes for myriad reasons including misfolding of a nascent chain or stalling of the ribosome during translation of mRNA. Clearance of a stalled complex is required to recycle the ribosome for future use. Here we show that the ubiquitin (Ub) pathway segregase Cdc48/p97 and its adaptors Ufd1-Npl4 participate in ribosome-associated degradation (RAD) by mediating the clearance of ubiquitinated, tRNA-linked nascent peptides from ribosomes. Through characterization of both endogenously-generated and heterologous model substrates for the RAD pathway, we conclude that budding yeast Cdc48 functions downstream of the Ub ligases Ltn1 and Ubr1 to release nascent proteins from the ribosome so that they can be degraded by the proteasome. Defective RAD could contribute to the pathophysiology of human diseases caused by mutations in p97.https://elifesciences.org/articles/00308ubiquitinribosomeCdc48 |
| spellingShingle | Rati Verma Robert S Oania Natalie J Kolawa Raymond J Deshaies Cdc48/p97 promotes degradation of aberrant nascent polypeptides bound to the ribosome eLife ubiquitin ribosome Cdc48 |
| title | Cdc48/p97 promotes degradation of aberrant nascent polypeptides bound to the ribosome |
| title_full | Cdc48/p97 promotes degradation of aberrant nascent polypeptides bound to the ribosome |
| title_fullStr | Cdc48/p97 promotes degradation of aberrant nascent polypeptides bound to the ribosome |
| title_full_unstemmed | Cdc48/p97 promotes degradation of aberrant nascent polypeptides bound to the ribosome |
| title_short | Cdc48/p97 promotes degradation of aberrant nascent polypeptides bound to the ribosome |
| title_sort | cdc48 p97 promotes degradation of aberrant nascent polypeptides bound to the ribosome |
| topic | ubiquitin ribosome Cdc48 |
| url | https://elifesciences.org/articles/00308 |
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