Caspase recruitment domain protein 6 is a microtubule-interacting protein that positively modulates NF-κB activation
| Autor: | Tak W. Mak, Almut Dufner, Scott Pownall |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Time Factors
CARD Signaling Adaptor Proteins Immunoprecipitation Protein Conformation Protein domain Apoptosis Biology Protein Serine-Threonine Kinases Transfection Microtubules Cell Line Mice Protein structure Receptor-Interacting Protein Serine-Threonine Kinase 2 Chlorocebus aethiops Animals Humans RNA Small Interfering Luciferases Death domain Adaptor Proteins Signal Transducing Multidisciplinary Kinase Reverse Transcriptase Polymerase Chain Reaction NF-kappa B RNA-Binding Proteins Biological Sciences NFKB1 Blotting Northern Molecular biology Immunohistochemistry Tumor Necrosis Factor Receptor-Associated Peptides and Proteins Cell biology Protein Structure Tertiary Nuclear Pore Complex Proteins Receptor-Interacting Protein Serine-Threonine Kinases COS Cells Mutation RNA Interference Signal transduction Protein Binding Signal Transduction |
| Popis: | Proteins containing a caspase recruitment domain (CARD) play pivotal roles in signal transduction leading to apoptosis and NF-κB activation and inflammation. Here we identify and characterize human and mouse CARD protein 6 (CARD6), CARD-containing proteins of unique structure. CARD6 associates with microtubules and interacts with receptor-interacting protein (RIP)-like interacting caspase-like apoptosis regulatory protein kinase (RICK), a CARD-containing member of the RIP family of protein kinases. These kinases are involved in multiple NF-κB signaling pathways important for innate and adaptive immune responses. Surprisingly, the CARDs of CARD6 and RICK were not required for their interaction; instead, mutational analysis revealed that the CARD of CARD6 negatively controls the association of these molecules. CARD6 also binds to RIP1, a RIP kinase homologue that lacks a CARD but contains a C-terminal death domain. Coexpression of RICK targets CARD6 to aggresomes via a mechanism that requires the CARD of RICK. Importantly, CARD6 expression has a synergistic effect on NF-κB activation induced by several independent signal transduction pathways. In summary, our results indicate that CARD6 is a regulator of NF-κB activation that modulates the functions of RIP kinase family members. |
| Databáze: | OpenAIRE |
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