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USP9X controls translation efficiency via deubiquitination of eukaryotic translation initiation factor 4A1

Controlling translation initiation is an efficient way to regulate gene expression at the post-transcriptional level. However, current knowledge regarding regulatory proteins and their modes of controlling translation initiation is still limited. In this study, we employed tandem affinity purificati...

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Autores principales: Li, Zengxia, Cheng, Zhao, Raghothama, Chaerkady, Cui, Zhaomeng, Liu, Kaiyu, Li, Xiaojing, Jiang, Chenxiao, Jiang, Wei, Tan, Minjia, Ni, Xiaohua, Pandey, Akhilesh, Liu, Jun O, Dang, Yongjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778534/
https://www.ncbi.nlm.nih.gov/pubmed/29228324
http://dx.doi.org/10.1093/nar/gkx1226
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author Li, Zengxia
Cheng, Zhao
Raghothama, Chaerkady
Cui, Zhaomeng
Liu, Kaiyu
Li, Xiaojing
Jiang, Chenxiao
Jiang, Wei
Tan, Minjia
Ni, Xiaohua
Pandey, Akhilesh
Liu, Jun O
Dang, Yongjun
author_facet Li, Zengxia
Cheng, Zhao
Raghothama, Chaerkady
Cui, Zhaomeng
Liu, Kaiyu
Li, Xiaojing
Jiang, Chenxiao
Jiang, Wei
Tan, Minjia
Ni, Xiaohua
Pandey, Akhilesh
Liu, Jun O
Dang, Yongjun
author_sort Li, Zengxia
collection PubMed
description Controlling translation initiation is an efficient way to regulate gene expression at the post-transcriptional level. However, current knowledge regarding regulatory proteins and their modes of controlling translation initiation is still limited. In this study, we employed tandem affinity purification and mass spectrometry to screen for unknown proteins associated with the translation initiation machinery. Ubiquitin specific peptidase 9, X-linked (USP9X), was identified as a novel binding partner, that interacts with the eukaryotic translation initiation factor 4B (eIF4B) in a mRNA-independent manner. USP9X-deficient cells presented significantly impaired nascent protein synthesis, cap-dependent translation initiation and cellular proliferation. USP9X can selectively alter the translation of pro-oncogenic mRNAs, such as c-Myc and XIAP. Moreover, we found that eIF4A1, which is primarily ubiquitinated at Lys-369, is the substrate of USP9X. USP9X dysfunction increases the ubiquitination of eIF4A1 and enhances its degradation. Our results provide evidence that USP9X is a novel regulator of the translation initiation process via deubiquitination of eIF4A1, which offers new insight in understanding the pivotal role of USP9X in human malignancies and neurodevelopmental disorders.
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spelling pubmed-57785342018-01-30 USP9X controls translation efficiency via deubiquitination of eukaryotic translation initiation factor 4A1 Li, Zengxia Cheng, Zhao Raghothama, Chaerkady Cui, Zhaomeng Liu, Kaiyu Li, Xiaojing Jiang, Chenxiao Jiang, Wei Tan, Minjia Ni, Xiaohua Pandey, Akhilesh Liu, Jun O Dang, Yongjun Nucleic Acids Res Molecular Biology Controlling translation initiation is an efficient way to regulate gene expression at the post-transcriptional level. However, current knowledge regarding regulatory proteins and their modes of controlling translation initiation is still limited. In this study, we employed tandem affinity purification and mass spectrometry to screen for unknown proteins associated with the translation initiation machinery. Ubiquitin specific peptidase 9, X-linked (USP9X), was identified as a novel binding partner, that interacts with the eukaryotic translation initiation factor 4B (eIF4B) in a mRNA-independent manner. USP9X-deficient cells presented significantly impaired nascent protein synthesis, cap-dependent translation initiation and cellular proliferation. USP9X can selectively alter the translation of pro-oncogenic mRNAs, such as c-Myc and XIAP. Moreover, we found that eIF4A1, which is primarily ubiquitinated at Lys-369, is the substrate of USP9X. USP9X dysfunction increases the ubiquitination of eIF4A1 and enhances its degradation. Our results provide evidence that USP9X is a novel regulator of the translation initiation process via deubiquitination of eIF4A1, which offers new insight in understanding the pivotal role of USP9X in human malignancies and neurodevelopmental disorders. Oxford University Press 2018-01-25 2017-12-08 /pmc/articles/PMC5778534/ /pubmed/29228324 http://dx.doi.org/10.1093/nar/gkx1226 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Molecular Biology
Li, Zengxia
Cheng, Zhao
Raghothama, Chaerkady
Cui, Zhaomeng
Liu, Kaiyu
Li, Xiaojing
Jiang, Chenxiao
Jiang, Wei
Tan, Minjia
Ni, Xiaohua
Pandey, Akhilesh
Liu, Jun O
Dang, Yongjun
USP9X controls translation efficiency via deubiquitination of eukaryotic translation initiation factor 4A1
title USP9X controls translation efficiency via deubiquitination of eukaryotic translation initiation factor 4A1
title_full USP9X controls translation efficiency via deubiquitination of eukaryotic translation initiation factor 4A1
title_fullStr USP9X controls translation efficiency via deubiquitination of eukaryotic translation initiation factor 4A1
title_full_unstemmed USP9X controls translation efficiency via deubiquitination of eukaryotic translation initiation factor 4A1
title_short USP9X controls translation efficiency via deubiquitination of eukaryotic translation initiation factor 4A1
title_sort usp9x controls translation efficiency via deubiquitination of eukaryotic translation initiation factor 4a1
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778534/
https://www.ncbi.nlm.nih.gov/pubmed/29228324
http://dx.doi.org/10.1093/nar/gkx1226
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