Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus
| Autor: | C. Bidoia, Kieran Wynne, Barbara Roe, Mohamed Ali Jarboui, Virginie Gautier, Giuliano Elia, William W. Hall, Elena Woods |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Proteomics
Nucleolus Immune Cells Immunology Ribosome biogenesis lcsh:Medicine HIV Infections Pathogenesis Biology Ribosome Jurkat cells Microbiology Mass Spectrometry Jurkat Cells Stable isotope labeling by amino acids in cell culture Virology Retroviruses Molecular Cell Biology Humans lcsh:Science Multidisciplinary T Cells Proteomic Databases Gene Expression Profiling lcsh:R Cellular Structures Cell biology Transport protein Biosynthetic Pathways Host-Pathogen Interaction Protein Transport Viral Classification Gene Expression Regulation Proteome Virulence Factors and Mechanisms HIV-1 lcsh:Q tat Gene Products Human Immunodeficiency Virus Cellular Types Protein Abundance Cell Nucleolus Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 11, p e48702 (2012) |
| ISSN: | 1932-6203 |
| Popis: | The trans-activator Tat protein is a viral regulatory protein essential for HIV-1 replication. Tat trafficks to the nucleoplasm and the nucleolus. The nucleolus, a highly dynamic and structured membrane-less sub-nuclear compartment, is the site of rRNA and ribosome biogenesis and is involved in numerous cellular functions including transcriptional regulation, cell cycle control and viral infection. Importantly, transient nucleolar trafficking of both Tat and HIV-1 viral transcripts are critical in HIV-1 replication, however, the role(s) of the nucleolus in HIV-1 replication remains unclear. To better understand how the interaction of Tat with the nucleolar machinery contributes to HIV-1 pathogenesis, we investigated the quantitative changes in the composition of the nucleolar proteome of Jurkat T-cells stably expressing HIV-1 Tat fused to a TAP tag. Using an organellar proteomic approach based on mass spectrometry, coupled with Stable Isotope Labelling in Cell culture (SILAC), we quantified 520 proteins, including 49 proteins showing significant changes in abundance in Jurkat T-cell nucleolus upon Tat expression. Numerous proteins exhibiting a fold change were well characterised Tat interactors and/or known to be critical for HIV-1 replication. This suggests that the spatial control and subcellular compartimentaliation of these cellular cofactors by Tat provide an additional layer of control for regulating cellular machinery involved in HIV-1 pathogenesis. Pathway analysis and network reconstruction revealed that Tat expression specifically resulted in the nucleolar enrichment of proteins collectively participating in ribosomal biogenesis, protein homeostasis, metabolic pathways including glycolytic, pentose phosphate, nucleotides and amino acids biosynthetic pathways, stress response, T-cell signaling pathways and genome integrity. We present here the first differential profiling of the nucleolar proteome of T-cells expressing HIV-1 Tat. We discuss how these proteins collectively participate in interconnected networks converging to adapt the nucleolus dynamic activities, which favor host biosynthetic activities and may contribute to create a cellular environment supporting robust HIV-1 production. |
| Databáze: | OpenAIRE |
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