GRAIL
| Autor: | Marie A. Hollenhorst, Claire Holness, C. Garrison Fathman, Niroshana Anandasabapathy, Christine M. Seroogy, Gregory S. Ford, Violette Paragas, Luis Soares, Debra Bloom, Heidi Skrenta |
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| Rok vydání: | 2003 |
| Předmět: |
0303 health sciences
biology medicine.medical_treatment T cell Immunology Endocytic cycle Molecular biology Ubiquitin ligase Immune tolerance 03 medical and health sciences 0302 clinical medicine Infectious Diseases Cytokine medicine.anatomical_structure Ubiquitin Gene expression biology.protein medicine Transcriptional regulation Immunology and Allergy 030304 developmental biology 030215 immunology |
| Zdroj: | Immunity. 18:535-547 |
| ISSN: | 1074-7613 |
| Popis: | T cell anergy may serve to limit autoreactive T cell responses. We examined early changes in gene expression after antigen-TCR signaling in the presence (activation) or absence (anergy) of B7 costimulation. Induced expression of GRAIL (gene related to anergy in lymphocytes) was observed in anergic CD4(+) T cells. GRAIL is a type I transmembrane protein that localizes to the endocytic pathway and bears homology to RING zinc-finger proteins. Ubiquitination studies in vitro support GRAIL function as an E3 ubiquitin ligase. Expression of GRAIL in retrovirally transduced T cell hybridomas dramatically limits activation-induced IL-2 and IL-4 production. Additional studies suggest that GRAIL E3 ubiquitin ligase activity and intact endocytic trafficking are critical for cytokine transcriptional regulation. Expression of GRAIL after an anergizing stimulus may result in ubiquitin-mediated regulation of proteins essential for mitogenic cytokine expression, thus positioning GRAIL as a key player in the induction of the anergic phenotype. |
| Databáze: | OpenAIRE |
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