ArticleMolecular and cellular biology2003
Overlapping signals for protein degradation and nuclear localization define a role for intrinsic RAG-2 nuclear uptake in dividing cells.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 38 citations in OpenAlex.
- Proximity-based proteomic profiling uncovers distinct interactome of human RAG1 and RAG2.Acta biochimica et biophysica Sinica · 2026Article
- Recognition motifs for importin 4 [(L)PPRS(G/P)P] and importin 5 [KP(K/Y)LV] binding, identified by bio-informatic simulation and experimentalComputational and structural biotechnology journal · 2022Article
- The RAG-2 Inhibitory Domain Gates Accessibility of the V(D)J Recombinase to Chromatin.Molecular and cellular biology · 2018Article
- The full-length interleukin-33 (FLIL33)-importin-5 interaction does not regulate nuclear localization of FLIL33 but controls its intracellular degradation.The Journal of biological chemistry · 2017Article
- Riches in RAGs: Revealing the V(D)J Recombinase through High-Resolution Structures.Trends in biochemical sciences · 2017Review
- Spatio-temporal regulation of RAG2 following genotoxic stress.DNA repair · 2015Article
- An autoregulatory mechanism imposes allosteric control on the V(D)J recombinase by histone H3 methylation.Cell reports · 2015Article
- Stimulated nuclear import by β-like importins.F1000prime reports · 2013Review
- Nuclear import by karyopherin-βs: recognition and inhibition.Biochimica et biophysica acta · 2011Review
- Elucidating the domain architecture and functions of non-core RAG1: the capacity of a non-core zinc-binding domain to function in nuclear import and nucleic acid binding.BMC biochemistry · 2011Article
- Coupling of V(D)J recombination to the cell cycle suppresses genomic instability and lymphoid tumorigenesis.Immunity · 2011Article
- Analysis of mutations from SCID and Omenn syndrome patients reveals the central role of the Rag2 PHD domain in regulating V(D)J recombination.The Journal of clinical investigation · 2010Article
- Temporal and spatial regulation of V(D)J recombination: interactions of extrinsic factors with the RAG complex.Advances in experimental medicine and biology · 2009Review
- Developmental separation of V(D)J recombinase expression and initiation of IgH recombination in B lineage progenitors in vivo.The Journal of experimental medicine · 2004Article
- B lineage-specific regulation of V(D)J recombinase activity is established in common lymphoid progenitors.The Journal of experimental medicine · 2004Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Expression of the recombinase proteins RAG-1 and RAG-2 is discordant: while RAG-1 is relatively long lived, RAG-2 is degraded periodically at the G(1)-S transition. Destruction of RAG-2 is mediated by a conserved interval in the recombination-dispensable region. The need for RAG-2 to reaccumulate in the nucleus at each cell division suggested the existence of an intrinsic RAG-2 nuclear localization signal (NLS). RAG-1 or RAG-2, expressed individually, is a nuclear protein. A screen for proteins that bind the recombination-dispensable region of RAG-2 identified the nuclear transport protein Importin 5. Mutation of residues 499 to 508 in RAG-2 abolished Importin 5 binding, nuclear accumulation, and periodic degradation of RAG-2. The Importin 5 binding site overlaps an NLS, defined by mutagenesis. RAG-1 rescued the localization of degradation-defective, RAG-2 NLS mutants; this required an intact RAG-1 NLS. Mutations in RAG-2 that abolish intrinsic nuclear accumulation but spare periodic degradation impaired recombination in cycling cells; induction of quiescence restored recombination to wild-type levels. Recombination defects were correlated with a cell cycle-dependent defect in the ability of RAG-1 to rescue localization of the RAG-2 mutants. These results suggest that the intrinsic RAG-2 NLS functions in the nuclear uptake of RAG-2 following its reexpression in cycling cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.