title: A novel translational regulation function for the simian virus 40 large-T antigen gene.
abstract: Cells use the interferon-induced, double-stranded-RNA-dependent protein kinase PKR as a defense against virus infections. Upon activation, PKR phosphorylates and thereby inactivates the protein synthesis initiation factor eIF-2, resulting in the cessation of protein synthesis. Viruses have evolved various strategies to counteract this cellular defense. In this paper, we show that simian virus 40 (SV40) large-T antigen can antagonize the translational inhibitory effect resulting from the activation of PKR in virus-infected cells. Unlike the situation with other virus-host cell interactions, SV40 large-T antigen does not block the activation of PKR, suggesting that SV40 counteracts the cellular antiviral response mediated by PKR at a step downstream of PKR activation. Mutational analysis of large-T antigen indicates that a domain located between amino acids 400 and 600 of large-T antigen is responsible for this function. These results define a novel translational regulatory function for the SV40 large-T antigen.
authors: Robert H. Lurie Cancer Center, Northwestern University Medical School, Chicago, Illinois 60611.
authors: P
authors: P
authors: Rajan
authors: S
authors: S
authors: Swaminathan
authors: J
authors: J
authors: Zhu
authors: C N
authors: CN
authors: Cole
authors: G
authors: G
authors: Barber
authors: M J
authors: MJ
authors: Tevethia
authors: B
authors: B
authors: Thimmapaya
mesh_terms: D000251:Adenosine Triphosphatases / Q000502:physiology; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics* / Q000502:physiology; D001483:Base Sequence; D004789:Enzyme Activation; D006801:Humans; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics; D013539:Simian virus 40 / Q000235:genetics*; D019892:eIF-2 Kinase
chemical_list: D000952:Antigens, Polyomavirus Transforming; D012367:RNA, Viral; C052835:adenovirus associated RNA; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; D000251:Adenosine Triphosphatases