A dual role for the API2 moiety in API2-MALT1-dependent NF-κB activation: heterotypic oligomerization and TRAF2 recruitment
| Autor: | Xiaohong Jin, J Swenson, Peter Kuffa, Peter C. Lucas, Dawn Kohrt, David S.L. Kim, Linda M. McAllister-Lucas, Katy Siu, Shufang Gu |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
TRAF2 Oncogene Proteins Fusion Immunoprecipitation Recombinant Fusion Proteins Ubiquitin-Protein Ligases Blotting Western Biology Transfection medicine.disease_cause Inhibitor of apoptosis Tacrolimus Cell Line Inhibitor of Apoptosis Proteins Genetics medicine Humans Moiety Binding site Luciferases Molecular Biology Mutation NF-kappa B TNF Receptor-Associated Factor 2 Fusion protein Baculoviral IAP Repeat-Containing 3 Protein Cell biology MALT1 G Protein-Coupled Inwardly-Rectifying Potassium Channels Biochemistry Dimerization Protein Binding |
| Zdroj: | Oncogene. 26:5643-5654 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1210342 |
| Popis: | Mucosa-associated lymphoid tissue (MALT) lymphoma is the most common extranodal lymphoid neoplasm. Chromosomal translocation t(11;18)(q21,q21) is found in 30% of gastric MALT lymphomas and is associated with a failure to respond to standard treatment and a tendency to disseminate. This translocation generates a chimeric protein composed of N-terminal sequences of Inhibitor of Apoptosis 2 (API2, also known as BIRC3 and cIAP2) fused to C-terminal sequences of MALT1. API2-MALT1 promotes cell survival and proliferation via activation of nuclear factor-kappaB (NF-kappaB). Here, we investigate the mechanism by which the API2 moiety contributes to NF-kappaB stimulation. We find that the API2 moiety mediates oligomerization of API2-MALT1 as well as interaction with tumor necrosis factor receptor-associated factor 2 (TRAF2). Surprisingly, oligomerization does not occur via homotypic interaction; rather, the API2 moiety of one monomer interacts with the MALT1 moiety of another monomer. Further, the specific region of the API2 moiety responsible for mediating oligomerization is distinct from that mediating TRAF2 binding. Although deletion or mutation of the TRAF2 binding site does not inhibit oligomerization, it does lead to dramatically decreased NF-kappaB activation. Deletion of both TRAF2 binding and oligomerization regions results in near-complete loss of NF-kappaB activation. Thus, API2 moiety-mediated heterotypic oligomerization and TRAF2 binding both contribute to maximal API2-MALT1-dependent NF-kappaB stimulation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|