RAG2 is down-regulated by cytoplasmic sequestration and ubiquitin-dependent degradation.
Periodic accumulation and degradation of RAG2 (recombination-activating gene 2) protein controls the cell-cycle-dependent V(D)J recombination of lymphocyte antigen receptor genes. Here we show the molecular mechanism of RAG2 degradation. The RAG2 protein is translocated from the nucleus to the cytoplasm and degraded through the ubiquitin/proteasome system. RAG2 translocation is mediated by the Thr-490 phosphorylation of RAG2. Inhibition of this phosphorylation by p27Kip1 stabilizes the RAG2 protein in the nucleus. These results suggest that RAG2 sequestration in the cytoplasm and its subsequent degradation by the ubiquitin/proteasome system upon entering the S phase is an integral part of G0/G1-specific V(D)J recombination.
Research Institute For Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278-0022, Japan. mizuta@rs.noda.tus.ac.jp
Ryushin
R
Mizuta
Midori
M
Mizuta
Shinsuke
S
Araki
Daisuke
D
Kitamura
D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000502:physiology; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D015536:Down-Regulation; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008840:Microfilament Proteins / Q000032:analysis; D009097:Multienzyme Complexes / Q000502:physiology; D009124:Muscle Proteins; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D011995:Recombination, Genetic; D025801:Ubiquitin / Q000378:metabolism*
D004268:DNA-Binding Proteins; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D008840:Microfilament Proteins; D009097:Multienzyme Complexes; D009124:Muscle Proteins; C499308:Rag2 protein, mouse; C058992:Tagln protein, mouse; D025801:Ubiquitin; C064655:V(D)J recombination activating protein 2; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex