Related Experiment Videos
RAG2 is down-regulated by cytoplasmic sequestration and ubiquitin-dependent degradation
Ryushin Mizuta1, Midori Mizuta, Shinsuke Araki
1Research Institute For Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278-0022, Japan. mizuta@rs.noda.tus.ac.jp
Abstract:
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.