Subcellular Relocalization of a Trans-acting Factor Regulates Xiap Ires-dependent Translation.
From: Apoptosis Research Centre, Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, K1H 8L1, Canada.
Molecular biology of the cell
- Publish Date: Apr 2007
- ISSN: 1059-1524
- Volume: 18
- Issue: 4
- Pages: 1302-11
- Medium: Print
- Language: English
- Citation (JAMA): Lewis Stephen M, Veyrier Anne, Hosszu Ungureanu Nicoleta, et al. Subcellular Relocalization of a Trans-acting Factor Regulates Xiap Ires-dependent Translation.. Mol. Biol. Cell Apr 2007;18:1302-11
Abstract
Translation of the X-linked inhibitor of apoptosis (XIAP) proceeds by internal ribosome entry site (IRES)-mediated initiation, a process that is physiologically important because XIAP expression is essential for cell survival under conditions of compromised cap-dependent translation, such as cellular stress. The regulation of internal initiation requires the interaction of IRES trans-acting factors (ITAFs) with the IRES element. We used RNA-affinity chromatography to identify XIAP ITAFs and isolated the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1). We find that hnRNP A1 interacts with XIAP IRES RNA both in vitro and in vivo and that hnRNP A1 negatively regulates XIAP IRES activity. Moreover, XIAP IRES-dependent translation is significantly reduced when hnRNP A1 accumulates in the cytoplasm. Osmotic shock, a cellular stress that causes cytoplasmic accumulation of hnRNP A1, also leads to a decrease in XIAP levels that is abrogated by knockdown of hnRNP A1 expression. These results suggest that the subcellular localization of hnRNP A1 is an important determinant of its ability to negatively regulate XIAP IRES activity, suggesting that the subcellular distribution of ITAFs plays a critical role in regulating IRES-dependent translation. Our findings demonstrate that cytoplasmic hnRNP A1 is a negative regulator of XIAP IRES-dependent translation, indicating a novel function for the cytoplasmic form of this protein.
Mesh Headings (Keywords): Amino Acid Sequence, Base Sequence, Binding Sites, Cells, Cultured, Chromatography, Affinity, Cytoplasm, Gene Expression Regulation, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Humans, Molecular Sequence Data, Osmotic Pressure, Protein Biosynthesis, Protein Transport, Ribosomes, Stress, X-Linked Inhibitor of Apoptosis Protein
Check for Full Text / PubMed Unique Identifier (PMID): 17287399
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.