TRAF-3 interacts with p62 nucleoporin, a component of the nuclear pore central plug that binds classical NLS-containing import complexes

Christopher Gamper, W. G. Van Eyndhoven, E. Schweiger, M. Mossbacher, B. Koo, S. Lederman

Research output: Contribution to journalArticle

Abstract

The TRAF-3 gene encodes a number of splice-variant isoforms that function as adapter molecules in NF-κB signaling, in part by associating with the cytoplasmic tails of CD40 or other TNF-receptor (TNF-R) family members. To identify downstream molecules in TRAF-3 signaling, a yeast two-hybrid library was screened with a full-length TRAF-3 construct. Nine independent TRAF-3 interacting clones encoded fragments of p62 Nucleoporin (p62), a 522 amino acid (aa) component of the nuclear pore central plug, that is known to bind karyopherin-β/classical-NLS import factor complexes. The interaction of p62 with TRAF-3 was specific, since p62 failed to interact with TRAF-2, -4, -5, or -6. Deletional analysis in yeast revealed that the p62:TRAF-3 interaction is mediated by a p62 carboxy (C)-terminal coiled-coil domain. In human 293 T cells, recombinant TRAF-3 or p62 specifically co-immunoprecipitates the other species. In addition, endogenous p62 co-precipitates over-expressed TRAF-3. The functional effects of over-expressing a TRAF-3 binding fragment, p62(aa 336-522) were studied on NF-κB-dependent, or control STAT1-dependent reporter activity in 293 T cells, either resting or after stimulation by CD40 or IFN-γ, respectively. Over-expression of p62(aa 336-522) induces NF-κB activation in resting cells and augments CD40-induced NF-κB activation, but has no effect on control STAT1 reporter activity, either at baseline or after IFN-γ induction. The finding that TRAF-3 binds p62, suggests that TRAF-3 may serve as an adapter molecule at the nuclear membrane, in addition to its known adapter function at the plasma membrane. (C) 2000 Elsevier Science Ltd. All rights reserved.

Original languageEnglish (US)
Pages (from-to)73-84
Number of pages12
JournalMolecular Immunology
Volume37
Issue number1-2
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Fingerprint

TNF Receptor-Associated Factor 3
Nuclear Pore
Amino Acids
nuclear pore protein p62
Yeasts
Karyopherins
T-Lymphocytes
Tumor Necrosis Factor Receptors
Nuclear Envelope
Libraries

Keywords

  • Cell surface molecules
  • Human
  • Molecular biology
  • Signal transduction
  • T cell-B cell collaboration

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

TRAF-3 interacts with p62 nucleoporin, a component of the nuclear pore central plug that binds classical NLS-containing import complexes. / Gamper, Christopher; Van Eyndhoven, W. G.; Schweiger, E.; Mossbacher, M.; Koo, B.; Lederman, S.

In: Molecular Immunology, Vol. 37, No. 1-2, 01.01.2000, p. 73-84.

Research output: Contribution to journalArticle

Gamper, Christopher ; Van Eyndhoven, W. G. ; Schweiger, E. ; Mossbacher, M. ; Koo, B. ; Lederman, S. / TRAF-3 interacts with p62 nucleoporin, a component of the nuclear pore central plug that binds classical NLS-containing import complexes. In: Molecular Immunology. 2000 ; Vol. 37, No. 1-2. pp. 73-84.
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