title: CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-kappa B.
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.
authors.affiliation: Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA. bertin@mpi.com
authors.forename: J
authors.initials: J
authors.lastname: Bertin
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: S M
authors.initials: SM
authors.lastname: Srinivasula
authors.forename: M D
authors.initials: MD
authors.lastname: Jacobson
authors.forename: J L
authors.initials: JL
authors.lastname: Poyet
authors.forename: S
authors.initials: S
authors.lastname: Merriam
authors.forename: M Q
authors.initials: MQ
authors.lastname: Du
authors.forename: M J
authors.initials: MJ
authors.lastname: Dyer
authors.forename: K E
authors.initials: KE
authors.lastname: Robison
authors.forename: P S
authors.initials: PS
authors.lastname: DiStefano
authors.forename: E S
authors.initials: ES
authors.lastname: Alnemri
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D000074018:B-Cell CLL-Lymphoma 10 Protein; D020169:Caspases / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C488088:Bcl10 protein, mouse; D016328:NF-kappa B; D011506:Proteins; D020169:Caspases