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Characterization of COMMD protein-protein interactions in NF-kappaB signalling.

Publication ,  Journal Article
de Bie, P; van de Sluis, B; Burstein, E; Duran, KJ; Berger, R; Duckett, CS; Wijmenga, C; Klomp, LWJ
Published in: Biochem J
August 15, 2006

COMMD [copper metabolism gene MURR1 (mouse U2af1-rs1 region 1) domain] proteins constitute a recently identified family of NF-kappaB (nuclear factor kappaB)-inhibiting proteins, characterized by the presence of the COMM domain. In the present paper, we report detailed investigation of the role of this protein family, and specifically the role of the COMM domain, in NF-kappaB signalling through characterization of protein-protein interactions involving COMMD proteins. The small ubiquitously expressed COMMD6 consists primarily of the COMM domain. Therefore COMMD1 and COMMD6 were analysed further as prototype members of the COMMD protein family. Using specific antisera, interaction between endogenous COMMD1 and COMMD6 is described. This interaction was verified by independent techniques, appeared to be direct and could be detected throughout the whole cell, including the nucleus. Both proteins inhibit TNF (tumour necrosis factor)-induced NF-kappaB activation in a non-synergistic manner. Mutation of the amino acid residues Trp24 and Pro41 in the COMM domain of COMMD6 completely abolished the inhibitory effect of COMMD6 on TNF-induced NF-kappaB activation, but this was not accompanied by loss of interaction with COMMD1, COMMD6 or the NF-kappaB subunit RelA. In contrast with COMMD1, COMMD6 does not bind to IkappaBalpha (inhibitory kappaBalpha), indicating that both proteins inhibit NF-kappaB in an overlapping, but not completely similar, manner. Taken together, these data support the significance of COMMD protein-protein interactions and provide new mechanistic insight into the function of this protein family in NF-kappaB signalling.

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Published In

Biochem J

DOI

EISSN

1470-8728

Publication Date

August 15, 2006

Volume

398

Issue

1

Start / End Page

63 / 71

Location

England

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Transcription Factor RelA
  • Signal Transduction
  • Sequence Alignment
  • RNA, Messenger
  • Proteins
  • Protein Binding
  • NF-kappa B
  • NF-KappaB Inhibitor alpha
  • Mutation
 

Citation

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de Bie, P., van de Sluis, B., Burstein, E., Duran, K. J., Berger, R., Duckett, C. S., … Klomp, L. W. J. (2006). Characterization of COMMD protein-protein interactions in NF-kappaB signalling. Biochem J, 398(1), 63–71. https://doi.org/10.1042/BJ20051664
Bie, Prim de, Bart van de Sluis, Ezra Burstein, Karen J. Duran, Ruud Berger, Colin S. Duckett, Cisca Wijmenga, and Leo W. J. Klomp. “Characterization of COMMD protein-protein interactions in NF-kappaB signalling.Biochem J 398, no. 1 (August 15, 2006): 63–71. https://doi.org/10.1042/BJ20051664.
de Bie P, van de Sluis B, Burstein E, Duran KJ, Berger R, Duckett CS, et al. Characterization of COMMD protein-protein interactions in NF-kappaB signalling. Biochem J. 2006 Aug 15;398(1):63–71.
de Bie, Prim, et al. “Characterization of COMMD protein-protein interactions in NF-kappaB signalling.Biochem J, vol. 398, no. 1, Aug. 2006, pp. 63–71. Pubmed, doi:10.1042/BJ20051664.
de Bie P, van de Sluis B, Burstein E, Duran KJ, Berger R, Duckett CS, Wijmenga C, Klomp LWJ. Characterization of COMMD protein-protein interactions in NF-kappaB signalling. Biochem J. 2006 Aug 15;398(1):63–71.

Published In

Biochem J

DOI

EISSN

1470-8728

Publication Date

August 15, 2006

Volume

398

Issue

1

Start / End Page

63 / 71

Location

England

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Transcription Factor RelA
  • Signal Transduction
  • Sequence Alignment
  • RNA, Messenger
  • Proteins
  • Protein Binding
  • NF-kappa B
  • NF-KappaB Inhibitor alpha
  • Mutation