TY - JOUR
T1 - The nucleoporin Nup96 is required for proper expression of interferon-regulated proteins and functions
AU - Faria, Ana M C
AU - Levay, Agata
AU - Wang, Yaming
AU - Kamphorst, Alice O.
AU - Rosa, Magda L P
AU - Nussenzveig, Daniel R.
AU - Balkan, Wayne
AU - Chook, Yuh Min
AU - Levy, David E.
AU - Fontoura, Beatriz M A
N1 - Funding Information:
We thank V. Nussenzweig and M.C. Nussenzweig for productive discussions and G. Blobel, J. Glavy, and T. Boehmer for antibodies. We thank the Live Cell Imaging Facility at UTSW and H. Shio for support with EM samples. We thank H. Valentine, E. Casas, W. Zhu, E. Rabelo, L. Nathanson, and C. Arana for assistance. This work was supported by NIH (R01 GM067159-01 to B.M.A.F.); Florida Biomedical Research Grant (04TSP-02 project II to B.M.A.F.); American Cancer Society Institutional Grant (IRG98-277 to B.M.A.F.); Stanley J. Glaser Biomedical Research Grant (700393 to B.M.A.F.); CNPq, FAPEMIG grants to A.M.C.F., and NIH (AI28900 to D.E.L.).
PY - 2006/3
Y1 - 2006/3
N2 - Nup98 and Nup96 are components of the nuclear transport machinery and are induced by interferons (IFN). Nup98 is a constituent of an mRNA export pathway that is targeted by viruses and regulated by IFN. However, the role of Nup96 in IFN-related mechanisms has not been established. To investigate the function of Nup96 in vivo, we generated Nup96+/- mice that express low levels of Nup96, as Nup96-/- mice are lethal. The Nup96+/- mice presented selective alterations of the immune system, which resulted in downregulation and impaired IFN α- and γ-mediated induction of MHC I and IFNγ induction of MHC II, ICAM-1, and other proteins. Frequency of TCRαβ+ and CD4+ T cells, which depends on MHC function, is reduced in NUP96+/- mice. Upon immunization, Nup96+/- mice showed impaired antigen presentation and T cell proliferation. Nup96+/- cells and mice were highly susceptible to viral infection, demonstrating a role for Nup96 in innate and adaptive immunity.
AB - Nup98 and Nup96 are components of the nuclear transport machinery and are induced by interferons (IFN). Nup98 is a constituent of an mRNA export pathway that is targeted by viruses and regulated by IFN. However, the role of Nup96 in IFN-related mechanisms has not been established. To investigate the function of Nup96 in vivo, we generated Nup96+/- mice that express low levels of Nup96, as Nup96-/- mice are lethal. The Nup96+/- mice presented selective alterations of the immune system, which resulted in downregulation and impaired IFN α- and γ-mediated induction of MHC I and IFNγ induction of MHC II, ICAM-1, and other proteins. Frequency of TCRαβ+ and CD4+ T cells, which depends on MHC function, is reduced in NUP96+/- mice. Upon immunization, Nup96+/- mice showed impaired antigen presentation and T cell proliferation. Nup96+/- cells and mice were highly susceptible to viral infection, demonstrating a role for Nup96 in innate and adaptive immunity.
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U2 - 10.1016/j.immuni.2006.01.014
DO - 10.1016/j.immuni.2006.01.014
M3 - Article
C2 - 16546098
AN - SCOPUS:33644988814
SN - 1074-7613
VL - 24
SP - 295
EP - 304
JO - Immunity
JF - Immunity
IS - 3
ER -