A Conserved Degradation Signal Regulates RAG-2 Accumulation during Cell Division and Links V(D)J Recombination to the Cell Cycle
| Autor: | Jinhak Lee, Zhong Li, Dominic Dordai, Stephen Desiderio |
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| Jazyk: | angličtina |
| Předmět: |
Periodicity
Cell division Molecular Sequence Data Immunology Immunoglobulin Variable Region Receptors Antigen T-Cell Mice Transgenic Thymus Gland Biology medicine.disease_cause Cell cycle phase Mice Structure-Activity Relationship Cyclin-dependent kinase medicine Animals Humans Immunology and Allergy Amino Acid Sequence Phosphorylation Nuclear protein T-Cell Receptor Beta Chain Immunoglobulin Fragments Recombination Genetic Mutation Genes Immunoglobulin Cell Cycle V(D)J recombination Nuclear Proteins Proteins Cell cycle Molecular biology Cyclin-Dependent Kinases Cell biology DNA-Binding Proteins Infectious Diseases biology.protein Immunoglobulin Joining Region Female Peptides Half-Life |
| Zdroj: | Immunity. (6):575-589 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/S1074-7613(00)80272-1 |
| Popis: | The proteins RAG-1 and RAG-2 are essential for initiation of V(D)J recombination. In dividing cells, RAG-2 accumulates during G1 and is undetectable during the S and G2/M cell cycle phases. A conserved degradation signal, including an essential CDK phosphorylation site at Thr-490, regulates RAG-2 accumulation during cell division and links V(D)J recombination to the cell cycle. Mutations within this signal abolish periodic degradation of RAG-2 protein in dividing cells. In mice expressing endogenous or wild-type transgenic RAG-2, V(D)J recombination intermediates accumulate preferentially in GO/G1 thymocytes; this restriction is relieved by mutation of Thr-490 to alanine (T490A). Thus, periodic destruction of RAG-2 protein couples V(D)J recombination to cell cycle phase. Using transgenic mice expressing the T490A RAG-2 mutant and a functional T cell receptor β chain, we demonstrate that coupling of V(D)J recombination to the cell cycle is not essential for enforcement of allelic exclusion. |
| Databáze: | OpenAIRE |
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