ArticleProceedings of the National Academy of Sciences of the United States of America2002
Mutagenesis of a functional chimeric gene in yeast identifies mutations in the simian virus 40 large T antigen J domain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Steered molecular dynamics simulation of the binding of the bovine auxilin J domain to the Hsc70 nucleotide-binding domain.Journal of molecular modeling · 2017Article
- Dihydropyrimidinones and -thiones with improved activity against human polyomavirus family members.Bioorganic & medicinal chemistry letters · 2016Article
- The conserved core enzymatic activities and the distinct dynamics of polyomavirus large T antigens.Archives of biochemistry and biophysics · 2015Article
- Synthesis and structure–activity relationships of small molecule inhibitors of the simian virus 40 T antigen oncoprotein, an anti-polyomaviral target.Bioorganic & medicinal chemistry · 2014Article
- Formation of covalently modified folding intermediates of simian virus 40 Vp1 in large T antigen-expressing cells.Journal of virology · 2013Article
- A screen for modulators of large T antigen's ATPase activity uncovers novel inhibitors of Simian Virus 40 and BK virus replication.Antiviral research · 2012Article
- Structure and mechanistic insights into novel iron-mediated moonlighting functions of human J-protein cochaperone, Dph4.The Journal of biological chemistry · 2012Article
- Multifaceted role of heat shock protein 70 in neurons.Molecular neurobiology · 2010Review
- Inhibition of Simian Virus 40 replication by targeting the molecular chaperone function and ATPase activity of T antigen.Virus research · 2009Article
- Association of simian virus 40 vp1 with 70-kilodalton heat shock proteins and viral tumor antigens.Journal of virology · 2009Article
- Structural basis of J cochaperone binding and regulation of Hsp70.Molecular cell · 2007Article
- Enterocyte proliferation and intestinal hyperplasia induced by simian virus 40 T antigen require a functional J domain.Journal of virology · 2007Article
- Article
- SV40 large T antigen targets multiple cellular pathways to elicit cellular transformation.Oncogene · 2005Review
- Genetic analysis of the polyomavirus DnaJ domain.Journal of virology · 2005Article
- Not all J domains are created equal: implications for the specificity of Hsp40-Hsp70 interactions.Protein science : a publication of the Protein Society · 2005Review
- Simian virus 40 T antigens and J domains: analysis of Hsp40 cochaperone functions in Escherichia coli.Journal of virology · 2003Article
- The carboxy terminus of simian virus 40 large T antigen is required to disrupt the yeast cell cycle.Journal of virology · 2002Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Simian virus 40 large T antigen contains an amino terminal J domain that catalyzes T antigen-mediated viral DNA replication and cellular transformation. To dissect the role of the J domain in these processes, we exploited the genetic tools available only in the yeast Saccharomyces cerevisiae to isolate 14 loss-of-function point mutations in the T antigen J domain. This screen also identified mutations that, when engineered into simian virus 40, resulted in T antigen mutants that were defective for the ability to support viral growth, to transform mammalian cells in culture, to dissociate the p130-E2F4 transcription factor complex, and to stimulate ATP hydrolysis by hsc70, a hallmark of J domain-containing molecular chaperones. These data correlate the chaperone activity of the T antigen J domain with its roles in viral infection and cellular transformation and support a model by which the viral J domain recruits the cytoplasmic hsc70 molecular chaperone in the host to rearrange multiprotein complexes implicated in replication and transformation. More generally, this study presents the use of a yeast screen to identify loss-of-function mutations in a mammalian virus and can serve as a widely applicable method to uncover domain functions of mammalian proteins for which there are yeast homologues with selectable mutant phenotypes.
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