CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-kappa B

J Biol Chem. 2000 Dec 29;275(52):41082-6. doi: 10.1074/jbc.C000726200.

Abstract

BCL10/CLAP is an activator of apoptosis and NF-kappaB signaling pathways and has been implicated in B cell lymphomas of mucosa-associated lymphoid tissue. Although its role in apoptosis remains to be determined, BCL10 likely activates NF-kappaB through the IKK complex in response to upstream stimuli. The N-terminal caspase recruitment domain (CARD) of BCL10 has been proposed to function as an activation domain that mediates homophilic interactions with an upstream CARD-containing NF-kappaB activator. To identify upstream signaling partners of BCL10, we performed a mammalian two-hybrid analysis and identified CARD9 as a novel CARD-containing protein that interacts selectively with the CARD activation domain of BCL10. When expressed in cells, CARD9 binds to BCL10 and activates NF-kappaB. Furthermore, endogenous CARD9 is found associated with BCL10 suggesting that both proteins form a pre-existing signaling complex within cells. CARD9 also self-associates and contains extensive coiled-coil motifs that may function as oligomerization domains. We propose here that CARD9 is an upstream activator of BCL10 and NF-kappaB signaling.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Apoptosis*
  • B-Cell CLL-Lymphoma 10 Protein
  • Caspases / metabolism*
  • Mice
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • Proteins / chemistry
  • Proteins / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • B-Cell CLL-Lymphoma 10 Protein
  • Bcl10 protein, mouse
  • NF-kappa B
  • Proteins
  • Caspases

Associated data

  • GENBANK/AF311287
  • GENBANK/AF311288