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

Zengxia Li, Zhao Cheng, Chaerkady Raghothama, Zhaomeng Cui, Kaiyu Liu, Xiaojing Li, Chenxiao Jiang, Wei Jiang, Minjia Tan, Xiaohua Ni, Akhilesh Pandey, Jun O. Liu, Yongjun Dang

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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 ubiq-uitination of eIF4A1 and enhances its degradation. Our results provide evidence that USP9X is a novel regulator of the translation initiation process via deu-biquitination of eIF4A1, which offers new insight in understanding the pivotal role of USP9X in human malignancies and neurodevelopmental disorders.

Original languageEnglish (US)
Pages (from-to)823-839
Number of pages17
JournalNucleic acids research
Volume46
Issue number2
DOIs
StatePublished - Jan 25 2018

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'USP9X controls translation efficiency via deubiquitination of eukaryotic translation initiation factor 4A1'. Together they form a unique fingerprint.

  • Cite this

    Li, Z., Cheng, Z., Raghothama, C., Cui, Z., Liu, K., Li, X., Jiang, C., Jiang, W., Tan, M., Ni, X., Pandey, A., Liu, J. O., & Dang, Y. (2018). USP9X controls translation efficiency via deubiquitination of eukaryotic translation initiation factor 4A1. Nucleic acids research, 46(2), 823-839. https://doi.org/10.1093/nar/gkx1226