CIPER, a novel NF kappaB-activating protein containing a caspase recruitment domain with homology to Herpesvirus-2 protein E10.
We have identified and characterized CIPER, a novel protein containing a caspase recruitment domain (CARD) in its N terminus and a C-terminal region rich in serine and threonine residues. The CARD of CIPER showed striking similarity to E10, a product of the equine herpesvirus-2. CIPER formed homodimers via its CARD and interacted with viral E10 but not with several apoptosis regulators containing CARDs including ARC, RAIDD, RICK, caspase-2, caspase-9, or Apaf-1. Expression of CIPER induced NF-kappaB activation, which was inhibited by dominant-negative NIK and a nonphosphorylable IkappaB-alpha mutant but not by dominant-negative RIP. Mutational analysis revealed that the N-terminal region of CIPER containing the CARD was sufficient and necessary for NF-kappaB-inducing activity. Point mutations in highly conserved residues in the CARD of CIPER disrupted the ability of CIPER to activate NF-kappaB and to form homodimers, indicating that the CARD is essential for NF-kappaB activation and dimerization. We propose that CIPER acts in a NIK-dependent pathway of NF-kappaB activation.
Koseki
T
T
Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Inohara
N
N
Chen
S
S
Carrio
R
R
Merino
J
J
Hottiger
M O
MO
Nabel
G J
GJ
Núñez
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G
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1; D000074018:B-Cell CLL-Lymphoma 10 Protein; D015152:Blotting, Northern; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D053143:Caspase 2; D053453:Caspase 9; D020169:Caspases / Q000737:chemistry / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000737:chemistry; D004789:Enzyme Activation; D020224:Expressed Sequence Tags; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D017354:Point Mutation; D011506:Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
C506592:APAF1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; C488088:Bcl10 protein, mouse; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011506:Proteins; C506433:CASP9 protein, human; C506434:Casp9 protein, mouse; D053143:Caspase 2; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans