Authors
Gautier, Virginie WGu, Lili
O'Donoghue, Niaobh
Pennington, Stephen
Sheehy, Noreen
Hall, William W
Affiliation
UCD-Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin (UCD), Belfield, Dublin 4, Ireland. virginie.gautier@ucd.ieIssue Date
2009MeSH
Amino Acid MotifsChromatography, Affinity
Gene Expression Regulation, Viral
Gene Regulatory Networks
HIV Infections
HIV-1
Host-Pathogen Interactions
Humans
Jurkat Cells
Mass Spectrometry
Nuclear Proteins
RNA Processing, Post-Transcriptional
RNA, Viral
tat Gene Products, Human Immunodeficiency Virus
Metadata
Show full item recordCitation
In vitro nuclear interactome of the HIV-1 Tat protein. 2009, 6:47 RetrovirologyJournal
RetrovirologyDOI
10.1186/1742-4690-6-47PubMed ID
19454010Abstract
BACKGROUND: One facet of the complexity underlying the biology of HIV-1 resides not only in its limited number of viral proteins, but in the extensive repertoire of cellular proteins they interact with and their higher-order assembly. HIV-1 encodes the regulatory protein Tat (86-101aa), which is essential for HIV-1 replication and primarily orchestrates HIV-1 provirus transcriptional regulation. Previous studies have demonstrated that Tat function is highly dependent on specific interactions with a range of cellular proteins. However they can only partially account for the intricate molecular mechanisms underlying the dynamics of proviral gene expression. To obtain a comprehensive nuclear interaction map of Tat in T-cells, we have designed a proteomic strategy based on affinity chromatography coupled with mass spectrometry. RESULTS: Our approach resulted in the identification of a total of 183 candidates as Tat nuclear partners, 90% of which have not been previously characterised. Subsequently we applied in silico analysis, to validate and characterise our dataset which revealed that the Tat nuclear interactome exhibits unique signature(s). First, motif composition analysis highlighted that our dataset is enriched for domains mediating protein, RNA and DNA interactions, and helicase and ATPase activities. Secondly, functional classification and network reconstruction clearly depicted Tat as a polyvalent protein adaptor and positioned Tat at the nexus of a densely interconnected interaction network involved in a range of biological processes which included gene expression regulation, RNA biogenesis, chromatin structure, chromosome organisation, DNA replication and nuclear architecture. CONCLUSION: We have completed the in vitro Tat nuclear interactome and have highlighted its modular network properties and particularly those involved in the coordination of gene expression by Tat. Ultimately, the highly specialised set of molecular interactions identified will provide a framework to further advance our understanding of the mechanisms of HIV-1 proviral gene silencing and activation.Language
enISSN
1742-4690ae974a485f413a2113503eed53cd6c53
10.1186/1742-4690-6-47
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