title: Suppression of viral replication by drs tumor suppressor via mTOR dependent pathway.
abstract: The drs gene is an apoptosis-inducing tumor suppressor. By using drs-knockout (KO) mouse embryonic fibroblasts (MEFs), we showed that drs is involved in the host defense against viral infection. In drs-KO MEFs infected with vesicular stomatitis virus, the viral replication and protein synthesis were markedly enhanced without the upregulation of the cellular protein synthesis. Phosphorylation of S6K, S6, 4EBP1 and TSC2 proteins was closely correlated with the enhanced viral replication in drs-KO MEFs. Drs protein could associate with stress-inducible GADD34 to form a complex with TSC1/2, which suppresses mTOR activity. These findings indicate that Drs suppresses viral replication via mTOR-dependent pathway.
authors: Division of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga, Japan.
authors: Yukihiro
authors: Y
authors: Tambe
authors: Naomi
authors: N
authors: Okuyama
authors: Tatsuya
authors: T
authors: Nakagawa
authors: Akifumi
authors: A
authors: Muramoto
authors: Masahiro
authors: M
authors: Hasebe
authors: Tokuhiro
authors: T
authors: Chano
authors: Hirokazu
authors: H
authors: Inoue
mesh_terms: D000818:Animals; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology; D014777:Virus Diseases / Q000276:immunology*; D014779:Virus Replication
chemical_list: D015852:Eukaryotic Initiation Factor-2; D008565:Membrane Proteins; C486298:Srpx protein, mouse; C000624654:Tsc2 protein, mouse; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; C513256:Ppp1r15a protein, mouse; D054645:Protein Phosphatase 1