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

J Bertin1, Y Guo, L Wang

  • 1Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA. bertin@mpi.com

The Journal of Biological Chemistry
|October 29, 2000
PubMed

Insights

Researchers identified CARD9 as a novel upstream activator of BCL10 (B-cell lymphoma 10) and NF-kappaB signaling. This discovery sheds light on the molecular mechanisms underlying B-cell lymphomas and apoptosis regulation.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Immunology

Background:

  • BCL10 (B-cell lymphoma 10) is a key regulator of apoptosis and NF-kappaB signaling pathways.
  • Dysregulation of BCL10 is implicated in mucosa-associated lymphoid tissue B-cell lymphomas.
  • The N-terminal caspase recruitment domain (CARD) of BCL10 is crucial for its function in protein interactions.

Purpose of the Study:

  • To identify novel upstream signaling partners of BCL10.
  • To elucidate the role of CARD9 in BCL10-mediated signaling.
  • To understand the molecular basis of NF-kappaB activation by BCL10.

Main Methods:

  • Mammalian two-hybrid analysis to identify BCL10 interacting proteins.
  • Co-immunoprecipitation to confirm protein-protein interactions.
  • Reporter assays to assess NF-kappaB activation.

Main Results:

  • CARD9 was identified as a novel CARD-containing protein interacting with BCL10's CARD domain.
  • CARD9 binds to BCL10 and activates NF-kappaB signaling when expressed in cells.
  • Endogenous CARD9 and BCL10 form a pre-existing signaling complex.
  • CARD9 self-associates and possesses coiled-coil motifs, suggesting oligomerization.

Conclusions:

  • CARD9 acts as an upstream activator of BCL10.
  • CARD9 is a novel component in the NF-kappaB signaling pathway.
  • The BCL10-CARD9 complex plays a significant role in cellular signaling.

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