Document Detail

A conserved degradation signal regulates RAG-2 accumulation during cell division and links V(D)J recombination to the cell cycle.
MedLine Citation:
PMID:  8986717     Owner:  NLM     Status:  MEDLINE    
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 G0/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 beta chain, we demonstrate that coupling of V(D)J recombination to the cell cycle is not essential for enforcement of allelic exclusion.
Z Li; D I Dordai; J Lee; S Desiderio
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Immunity     Volume:  5     ISSN:  1074-7613     ISO Abbreviation:  Immunity     Publication Date:  1996 Dec 
Date Detail:
Created Date:  1997-01-30     Completed Date:  1997-01-30     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9432918     Medline TA:  Immunity     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  575-89     Citation Subset:  IM    
Department of Molecular Biology and Genetics, John Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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MeSH Terms
Amino Acid Sequence
Cell Cycle / physiology*
Cyclin-Dependent Kinases / metabolism
DNA-Binding Proteins*
Genes, Immunoglobulin*
Immunoglobulin Fragments / genetics*
Immunoglobulin Joining Region / genetics
Immunoglobulin Variable Region / genetics
Mice, Transgenic
Molecular Sequence Data
Nuclear Proteins
Peptides / metabolism
Proteins / metabolism*
Receptors, Antigen, T-Cell
Recombination, Genetic*
Structure-Activity Relationship
Thymus Gland / cytology,  metabolism
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Immunoglobulin Fragments; 0/Immunoglobulin Joining Region; 0/Immunoglobulin Variable Region; 0/Nuclear Proteins; 0/Peptides; 0/Proteins; 0/RAG2 protein, human; 0/Rag2 protein, mouse; 0/Receptors, Antigen, T-Cell; 0/V(D)J recombination activating protein 2; EC Kinases

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