Characterization of COMMD protein-protein interactions in NF-κB signalling

Prim De Bie, Bart Van De Sluis, Ezra Burstein, Karen J. Duran, Ruud Berger, Colin S. Duckett, Cisca Wijmenga, Leo W J Klomp

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

COMMD [copper metabolism gene MURR1 (mouse U2af1-rs1 region 1) domain] proteins constitute a recently identified family of NF-κB (nuclear factor κB)-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-κB 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-κB activation in a non-synergistic manner. Mutation of the amino acid residues Trp24 and Pro 41 in the COMM domain of COMMD6 completely abolished the inhibitory effect of COMMD6 on TNF-induced NF-κB activation, but this was not accompanied by loss of interaction with COMMD1, COMMD6 or the NF-κB subunit RelA. In contrast with COMMD1, COMMD6 does not bind to IκBα (inhibitory κBα), indicating that both proteins inhibit NF-κB 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-κB signalling.

Original languageEnglish (US)
Pages (from-to)63-71
Number of pages9
JournalBiochemical Journal
Volume398
Issue number1
DOIs
StatePublished - Aug 15 2006

Fingerprint

Proteins
Nuclear Family
Tumor Necrosis Factor-alpha
Chemical activation
Nuclear Proteins
Cell Nucleus
Metabolism
Immune Sera
Copper
Genes
Amino Acids
Mutation

Keywords

  • Copper
  • Copper metabolism gene MURR1 domain protein 6 (COMMD6)
  • Mouse U2af1-rs1 region 1 (MURR1)
  • Nuclear factor κB (NF-κB)
  • Protein-protein interaction

ASJC Scopus subject areas

  • Biochemistry

Cite this

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-κB signalling. Biochemical Journal, 398(1), 63-71. https://doi.org/10.1042/BJ20051664

Characterization of COMMD protein-protein interactions in NF-κB signalling. / De Bie, Prim; Van De Sluis, Bart; Burstein, Ezra; Duran, Karen J.; Berger, Ruud; Duckett, Colin S.; Wijmenga, Cisca; Klomp, Leo W J.

In: Biochemical Journal, Vol. 398, No. 1, 15.08.2006, p. 63-71.

Research output: Contribution to journalArticle

De Bie, P, Van De Sluis, B, Burstein, E, Duran, KJ, Berger, R, Duckett, CS, Wijmenga, C & Klomp, LWJ 2006, 'Characterization of COMMD protein-protein interactions in NF-κB signalling', Biochemical Journal, vol. 398, no. 1, pp. 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-κB signalling. Biochemical Journal. 2006 Aug 15;398(1):63-71. https://doi.org/10.1042/BJ20051664
De Bie, Prim ; Van De Sluis, Bart ; Burstein, Ezra ; Duran, Karen J. ; Berger, Ruud ; Duckett, Colin S. ; Wijmenga, Cisca ; Klomp, Leo W J. / Characterization of COMMD protein-protein interactions in NF-κB signalling. In: Biochemical Journal. 2006 ; Vol. 398, No. 1. pp. 63-71.
@article{668aa0037f2c41fe921d49dbc8d13f82,
title = "Characterization of COMMD protein-protein interactions in NF-κB signalling",
abstract = "COMMD [copper metabolism gene MURR1 (mouse U2af1-rs1 region 1) domain] proteins constitute a recently identified family of NF-κB (nuclear factor κB)-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-κB 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-κB activation in a non-synergistic manner. Mutation of the amino acid residues Trp24 and Pro 41 in the COMM domain of COMMD6 completely abolished the inhibitory effect of COMMD6 on TNF-induced NF-κB activation, but this was not accompanied by loss of interaction with COMMD1, COMMD6 or the NF-κB subunit RelA. In contrast with COMMD1, COMMD6 does not bind to IκBα (inhibitory κBα), indicating that both proteins inhibit NF-κB 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-κB signalling.",
keywords = "Copper, Copper metabolism gene MURR1 domain protein 6 (COMMD6), Mouse U2af1-rs1 region 1 (MURR1), Nuclear factor κB (NF-κB), Protein-protein interaction",
author = "{De Bie}, Prim and {Van De Sluis}, Bart and Ezra Burstein and Duran, {Karen J.} and Ruud Berger and Duckett, {Colin S.} and Cisca Wijmenga and Klomp, {Leo W J}",
year = "2006",
month = "8",
day = "15",
doi = "10.1042/BJ20051664",
language = "English (US)",
volume = "398",
pages = "63--71",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "1",

}

TY - JOUR

T1 - Characterization of COMMD protein-protein interactions in NF-κB signalling

AU - De Bie, Prim

AU - Van De Sluis, Bart

AU - Burstein, Ezra

AU - Duran, Karen J.

AU - Berger, Ruud

AU - Duckett, Colin S.

AU - Wijmenga, Cisca

AU - Klomp, Leo W J

PY - 2006/8/15

Y1 - 2006/8/15

N2 - COMMD [copper metabolism gene MURR1 (mouse U2af1-rs1 region 1) domain] proteins constitute a recently identified family of NF-κB (nuclear factor κB)-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-κB 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-κB activation in a non-synergistic manner. Mutation of the amino acid residues Trp24 and Pro 41 in the COMM domain of COMMD6 completely abolished the inhibitory effect of COMMD6 on TNF-induced NF-κB activation, but this was not accompanied by loss of interaction with COMMD1, COMMD6 or the NF-κB subunit RelA. In contrast with COMMD1, COMMD6 does not bind to IκBα (inhibitory κBα), indicating that both proteins inhibit NF-κB 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-κB signalling.

AB - COMMD [copper metabolism gene MURR1 (mouse U2af1-rs1 region 1) domain] proteins constitute a recently identified family of NF-κB (nuclear factor κB)-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-κB 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-κB activation in a non-synergistic manner. Mutation of the amino acid residues Trp24 and Pro 41 in the COMM domain of COMMD6 completely abolished the inhibitory effect of COMMD6 on TNF-induced NF-κB activation, but this was not accompanied by loss of interaction with COMMD1, COMMD6 or the NF-κB subunit RelA. In contrast with COMMD1, COMMD6 does not bind to IκBα (inhibitory κBα), indicating that both proteins inhibit NF-κB 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-κB signalling.

KW - Copper

KW - Copper metabolism gene MURR1 domain protein 6 (COMMD6)

KW - Mouse U2af1-rs1 region 1 (MURR1)

KW - Nuclear factor κB (NF-κB)

KW - Protein-protein interaction

UR - http://www.scopus.com/inward/record.url?scp=33747185438&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33747185438&partnerID=8YFLogxK

U2 - 10.1042/BJ20051664

DO - 10.1042/BJ20051664

M3 - Article

VL - 398

SP - 63

EP - 71

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 1

ER -