J Biol Chem. 2002 Apr 19;277(16):13952-8. Epub 2002 Jan 30.
CARD-8 protein, a new CARD family member that regulates caspase-1 activation and apoptosis.
Razmara, M., Srinivasula, S. M., Wang, L., Poyet, J. L., Geddes, B. J., DiStefano, P. S., Bertin, J., Alnemri, E. S.,
--- - Center for Apoptosis Research and the Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
--- - Center for Apoptosis Research and the Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Caspase-associated recruitment domains (CARD) are protein-protein interaction modules found extensively in proteins that play important roles in apoptosis, NFkappaB activation, and cytokine regulation. In this study we identified a novel human protein, CARD-8, which contains a C-terminal CARD domain with high similarity to the CARD domain of caspase-1/ICE. We demonstrate that CARD-8 interacts physically with caspase-1 and negatively regulates caspase-1-dependent IL-1beta generation in the THP-1 monocytic cell line. CARD-8 binds also to ICEBERG and pseudo-ICE, two other recently identified proteins, which bind to the CARD domain of caspase-1 and negatively regulate its activity. Reverse transcriptase-PCR analysis revealed that CARD-8 is expressed mainly in monocytes, placenta, lymph nodes, and spleen. This pattern of expression is consistent with caspase-1 expression in the same cells and tissues. CARD-8 was also found to negatively regulate NF-kappaB activation by TNF-alpha stimulation and by ectopically expressed RICK, suggesting that this protein may control cell survival. Consistent with these results, stable expression of CARD-8 in U937 or THP-1 cells sensitizes the cells to differentiation-induced apoptosis. Overexpression of CARD-8 can also induce apoptosis in transfected cells. The results suggest that CARD-8 represents a new signaling molecule involved in the regulation of caspase-1 and NF-kappaB activation.
PMID: 11821383

![]() ![]() ![]() ![]() |
![]() |
In vitro interaction | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
DD1 | DD2 | Reference | |||||||||||
Family | DD1 | DD2 | Method | Species | Region | Expression | Species | Region | Expression | ||||
CARD | Apaf1 |
![]() |
Caspase9 | GST fusion protein pull-down | Not specified | Not specified | E.coli | Not specified | Not specified | In vitro translation | 11821383 | ||
CARD | CARD16 |
![]() |
CARD8 | GST fusion protein pull-down | Not specified | Not specified | In vitro translation | Not specified | Full length | E.coli | 11821383 | ||
CARD | CARD16 |
![]() |
Caspase1 | GST fusion protein pull-down | Not specified | Not specified | E.coli | Not specified | Not specified | In vitro translation | 11821383 | ||
CARD | CARD18 |
![]() |
CARD8 | GST fusion protein pull-down | Not specified | Not specified | In vitro translation | Not specified | Full length | E.coli | 11821383 | ||
CARD | CARD8 |
![]() |
Caspase1 | GST fusion protein pull-down | Not specified | Full length | E.coli | Not specified | Not specified | In vitro translation | 11821383 |
(
: click this icon to show interactions only between the two corresponding DDs)

![]() ![]() ![]() ![]() |
![]() |
In vivo interaction | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Endogenous expression |
Overexpression | DD1 | DD2 | Reference | |||||||||
Family | DD1 | DD2 | Method | Species | Region | Species | Region | ||||||
CARD | CARD16 |
![]() |
CARD8 | Co-immunoprecipitation | HEK293 | Not specified | Full length | Not specified | Not specified | 11821383 | |||
CARD | CARD16 |
![]() |
CARD8 | Co-immunoprecipitation | HEK293 | Not specified | Not specified | Not specified | Full length | 11821383 | |||
CARD | CARD8 |
![]() |
Caspase1 | Co-immunoprecipitation | HEK293 | Not specified | Full length | Not specified | Not specified | 11821383 | |||
CARD | CARD8 |
![]() |
Caspase1 | Co-immunoprecipitation | HEK293 | Not specified | Not specified | Not specified | Full length | 11821383 |
(
: click this icon to show interactions only between the two corresponding DDs)

![]() ![]() ![]() ![]() |
![]() |
Functional Role | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Family | DD1 | DD2 | Method | Death-related | Death-unrelated | Reference | |||||
CARD | CARD8 |
![]() |
Caspase1 | Caspase cleaved assay, ELISA | Caspase1 activation block, IL-1b secretion decrease | 11821383 |
(
: click this icon to show interactions only between the two corresponding DDs)
