TRAF7 protein promotes Lys-29-linked polyubiquitination of IκB kinase (IKKγ)/NF-κB essential modulator (NEMO) and p65/RelA protein and represses NF-κB activation

Tiziana Zotti, Antonio Uva, Angela Ferravante, Mariangela Vessichelli, Ivan Scudiero, Michele Ceccarelli, Pasquale Vito, Romania Stilo

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Tumor necrosis factor receptor-associated factor (TRAF) proteins are cytoplasmic regulatory molecules that function as signal transducers for receptors involved in both innate and adaptive humoral immune responses. In this study, we show that TRAF7, the unique noncanonical member of the TRAF family, physically associates with IκB kinase/NF-κB essential modulator (NEMO) and with the RelA/p65 (p65) member of the NF-κB transcription factor family. TRAF7 promotes Lys-29-linked polyubiquitination of NEMO and p65 that results in lysosomal degradation of both proteins and altered activation. TRAF7 also influences p65 nuclear distribution. Microarray expression data are consistent with an inhibitory role for TRAF7 on NF-κB and a positive control of AP-1 transcription factor. Finally, functional data indicate that TRAF7 promotes cell death. Thus, this study identifies TRAF7 as a NEMO- and p65-interacting molecule and brings important information on the ubiquitination events that control NF-κB transcriptional activity.

Original languageEnglish
Pages (from-to)22924-22933
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number26
DOIs
Publication statusPublished - 1 Jul 2011
Externally publishedYes

Fingerprint

Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Modulators
Phosphotransferases
Chemical activation
Ubiquitination
Transcription Factor AP-1
Adaptive Immunity
Humoral Immunity
Transducers
Proteolysis
Proteins
Molecules
Cell Death
Transcription Factors
Cell death
Microarrays
Degradation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

TRAF7 protein promotes Lys-29-linked polyubiquitination of IκB kinase (IKKγ)/NF-κB essential modulator (NEMO) and p65/RelA protein and represses NF-κB activation. / Zotti, Tiziana; Uva, Antonio; Ferravante, Angela; Vessichelli, Mariangela; Scudiero, Ivan; Ceccarelli, Michele; Vito, Pasquale; Stilo, Romania.

In: Journal of Biological Chemistry, Vol. 286, No. 26, 01.07.2011, p. 22924-22933.

Research output: Contribution to journalArticle

Zotti, Tiziana ; Uva, Antonio ; Ferravante, Angela ; Vessichelli, Mariangela ; Scudiero, Ivan ; Ceccarelli, Michele ; Vito, Pasquale ; Stilo, Romania. / TRAF7 protein promotes Lys-29-linked polyubiquitination of IκB kinase (IKKγ)/NF-κB essential modulator (NEMO) and p65/RelA protein and represses NF-κB activation. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 26. pp. 22924-22933.
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AB - Tumor necrosis factor receptor-associated factor (TRAF) proteins are cytoplasmic regulatory molecules that function as signal transducers for receptors involved in both innate and adaptive humoral immune responses. In this study, we show that TRAF7, the unique noncanonical member of the TRAF family, physically associates with IκB kinase/NF-κB essential modulator (NEMO) and with the RelA/p65 (p65) member of the NF-κB transcription factor family. TRAF7 promotes Lys-29-linked polyubiquitination of NEMO and p65 that results in lysosomal degradation of both proteins and altered activation. TRAF7 also influences p65 nuclear distribution. Microarray expression data are consistent with an inhibitory role for TRAF7 on NF-κB and a positive control of AP-1 transcription factor. Finally, functional data indicate that TRAF7 promotes cell death. Thus, this study identifies TRAF7 as a NEMO- and p65-interacting molecule and brings important information on the ubiquitination events that control NF-κB transcriptional activity.

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