Inhibitor of apoptosis protein from Orgyia pseudotsugata nuclear polyhedrosis virus provides a costimulatory signal required for optimal proliferation of developing thymocytes.
The inhibitors of apoptosis proteins (IAPs) constitute a family of endogenous inhibitors that control apoptosis in the cell by inhibiting caspase processing and activity. IAPs are also implicated in cell division, cell cycle regulation, and cancer. To address the role of IAPs in thymus development and homeostasis, we generated transgenic mice expressing IAP generated from the baculovirus Orgyia pseudotsugata nuclear polyhedrosis virus (OpIAP). Developing thymocytes expressing OpIAP show increased nuclear levels of NF-kappaB and reduced cytoplasmic levels of its inhibitor, IkappaBalpha. In mature thymocytes, OpIAP induces optimal activation and proliferation after TCR triggering in the absence of a costimulatory signal. OpIAP expression in immature thymocytes blocks TCR-induced apoptosis. Taken together, our data illustrate the pleiotropism of OpIAP in vivo.
Robles
María S
MS
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Universidad Autónoma de Madrid, Madrid Campus de Cantoblanco, Madrid, Spain. msrobles@cnb.uam.es
Leonardo
Esther
E
Criado
Luis Miguel
LM
Izquierdo
Manuel
M
Martínez-A
Carlos
C
D000818:Animals; D017209:Apoptosis; D017252:CD3 Complex / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism; D020672:I-kappa B Proteins; D051034:Inhibitor of Apoptosis Proteins; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D017924:Nucleopolyhedroviruses; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000254:growth & development / Q000276:immunology*
D017252:CD3 Complex; D016207:Cytokines; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D000072000:NF-KappaB Inhibitor alpha; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)