The nucleoporin Nup96 is required for proper expression of interferon-regulated proteins and functions

Ana M C Faria, Agata Levay, Yaming Wang, Alice O. Kamphorst, Magda L P Rosa, Daniel R. Nussenzveig, Wayne Balkan, Yuh Min Chook, David E. Levy, Beatriz M A Fontoura

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)295-304
Number of pages10
JournalImmunity
Volume24
Issue number3
DOIs
StatePublished - Mar 2006

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Interferons
Proteins
nuclear pore complex protein 96
T-Lymphocytes
Cell Nucleus Active Transport
Antigen Presentation
Adaptive Immunity
Virus Diseases
Intercellular Adhesion Molecule-1
Innate Immunity
Immune System
Immunization
Down-Regulation
Cell Proliferation
Viruses
Messenger RNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

The nucleoporin Nup96 is required for proper expression of interferon-regulated proteins and functions. / Faria, Ana M C; Levay, Agata; Wang, Yaming; Kamphorst, Alice O.; Rosa, Magda L P; Nussenzveig, Daniel R.; Balkan, Wayne; Chook, Yuh Min; Levy, David E.; Fontoura, Beatriz M A.

In: Immunity, Vol. 24, No. 3, 03.2006, p. 295-304.

Research output: Contribution to journalArticle

Faria, Ana M C ; Levay, Agata ; Wang, Yaming ; Kamphorst, Alice O. ; Rosa, Magda L P ; Nussenzveig, Daniel R. ; Balkan, Wayne ; Chook, Yuh Min ; Levy, David E. ; Fontoura, Beatriz M A. / The nucleoporin Nup96 is required for proper expression of interferon-regulated proteins and functions. In: Immunity. 2006 ; Vol. 24, No. 3. pp. 295-304.
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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

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