Cell cycle regulation of V(D)J recombination-activating protein RAG-2.
The antigen receptors of B and T lymphocytes are encoded in multiple germ-line DNA segments that are joined during lymphocyte development. The recombination-activating proteins RAG-1 and RAG-2 are both essential for this process, termed V(D)J rearrangement. Phosphorylation of the RAG-2 protein at Thr-490 by one or more cyclin-dependent kinases is associated with its rapid degradation. In an immature B-cell line and in normal thymocytes, RAG-2 protein accumulates preferentially in the G0/G1 phases of the cell cycle and declines by at least 20-fold before cells enter S phase. The amount of RAG-2 protein remains low throughout the S, G2, and M phases. The amount of RAG-1 protein shows considerably less fluctuation. The variation in RAG-2 protein is likely to be established, at least in part, by a posttranscriptional mechanism. These observations suggest that V(D)J rearrangement occurs entirely or preferentially within G0/G1.
Lin
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Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
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D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D004268:DNA-Binding Proteins; D005434:Flow Cytometry; D016193:G1 Phase / Q000502:physiology; D005786:Gene Expression Regulation; D015322:Gene Rearrangement, B-Lymphocyte; D006412:Hematopoietic Stem Cells; D051379:Mice; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D016192:Resting Phase, Cell Cycle / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*
D004268:DNA-Binding Proteins; D011506:Proteins; D012333:RNA, Messenger; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2