An unexpected functional link between lysosomal thiol reductase and mitochondrial manganese superoxide dismutase.
Gamma interferon-inducible thiol reductase (GILT) is an enzyme involved in the initial steps of antigen processing and presentation. Recently we have shown that GILT is also expressed in mouse T cells, where it exerts an inhibitory role on T cell activation. In this study, we identified mitochondrial manganese superoxide dismutase (SOD2) as one of the key intermediaries affected by GILT expression in fibroblasts. Expression and activity of SOD2 is reduced in the absence of GILT because of reduced SOD2 protein stability. The forced increase in SOD2 expression in the absence of GILT restores fibroblast proliferation to wild-type levels. Thus, GILT appears to have a fundamental role in cellular proliferation mediated through its influence on SOD2 protein activity and expression.
Bogunovic
Branka
B
Department of Microbiology and Immunology, Georgetown University, 3900 Reservoir Road NW, Washington, DC 20057, USA.
Stojakovic
Milica
M
Chen
Leonard
L
Maric
Maja
M
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D004795:Enzyme Stability / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D050862:Oxidoreductases Acting on Sulfur Group Donors; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology*; D000099156:Superoxide Dismutase 2
D024101:Mitochondrial Proteins; D010088:Oxidoreductases; D050862:Oxidoreductases Acting on Sulfur Group Donors; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C483811:Ifi30 protein, mouse