Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 285, Issue 32, Pages 24372-24380Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M109.100057
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Funding
- National Institutes of Health [RO1AI060919]
- Welch Foundation [I-1389]
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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 CC2D1A is a potent activator of NF-kappa B. The activation of NF-kappa B by CC2D1A requires its C2 domain. CC2D1A activates NF-kappa B in a manner that depends on the ubiquitin-conjugating enzyme Ubc13, TNF receptor-associated factor TRAF2, the protein kinase TAK1, and the I kappa B kinase (IKK) complex. In addition, the deubiquitination enzyme Cylindromatosis (CYLD) negatively regulates the activity of CC2D1A. These results suggest that CC2D1A activates NF-kappa B through the canonical IKK pathway.
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