CC2D1A, a DM14 and C2 domain protein, activates NF-κB through the canonical pathway

Meng Zhao, Xiao Dong Li, Zhijian Chen

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

CC2D1A is an evolutionarily conserved protein that contains four DM14 domains at the N terminus and a C2 domain at the C terminus. Loss-of-function mutations in CC2D1A have been linked to mental retardation in human, but the biochemical function of this protein is largely unknown. Here, we show that CC2D1Ais a potent activator of NF-κB. The activation of NF-κB by CC2D1A requires its C2 domain. CC2D1A activates NF-κB in a manner that depends on the ubiquitin-conjugating enzyme Ubc13, TNF receptor-associated factor TRAF2, the protein kinase TAK1, and the IκB kinase (IKK) complex. In addition, the deubiquitination enzyme Cylindromatosis (CYLD) negatively regulates the activity of CC2D1A. These results suggest that CC2D1A activates NF-κB through the canonical IKK pathway.

Original languageEnglish (US)
Pages (from-to)24372-24380
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number32
DOIs
StatePublished - Aug 6 2010

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TNF Receptor-Associated Factor 2
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Ubiquitin-Conjugating Enzymes
Intellectual Disability
Protein Kinases
Proteins
Phosphotransferases
Chemical activation
Mutation
Enzymes
C2 Domains

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

CC2D1A, a DM14 and C2 domain protein, activates NF-κB through the canonical pathway. / Zhao, Meng; Li, Xiao Dong; Chen, Zhijian.

In: Journal of Biological Chemistry, Vol. 285, No. 32, 06.08.2010, p. 24372-24380.

Research output: Contribution to journalArticle

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