J Biol Chem. 2000 Dec 29;275(52):41082-6.

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

Bertin, J., Guo, Y., Wang, L., Srinivasula, S. M., Jacobson, M. D., Poyet, J. L., Merriam, S., Du, M. Q., Dyer, M. J., Robison, K. E., DiStefano, P. S., Alnemri, E. S.,
--- - Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA. bertin@mpi.com
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.
PMID: 11053425External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vitro interaction
  DD1 DD2 Reference
Family DD1 DD2 Method Species Region Expression Species Region Expression
CARD Bcl-10 Link CARD9 GST fusion protein pull-down Herpesvirus2 Not specified E.coli Human Full length In vitro translation 11053425
CARD Bcl-10 Link CARD9 Two-hybrid Not specified 1-104 HEK293 Human 1-110 HEK293 11053425
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
CARD Bcl-10 Link CARD9 Co-Immunofluorescence staining Rat-1 cell Herpesvirus2 Full length Human Full length 11053425
CARD Bcl-10 Link CARD9 Co-immunoprecipitation HEK293 Herpesvirus2 Not specified Human Full length 11053425
CARD Bcl-10 Link CARD9 Co-immunoprecipitation HEK293 11053425
CARD CARD9 Link CARD9 Co-immunoprecipitation HEK293 Human Full length Human Full length 11053425
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
CARD Bcl-10 Link CARD9 Luciferase assay NF-kB activation (signalosome) 11053425
(Link: click this icon to show interactions only between the two corresponding DDs)