Evidence map›Paper›PMID 12861017›Full record

ArticleMolecular and cellular biology2003

Overlapping signals for protein degradation and nuclear localization define a role for intrinsic RAG-2 nuclear uptake in dividing cells.

Ashley E Ross, Milena Vuica, Stephen Desiderio

Open access · greenAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.4field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 38 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Ashley E RossDepartment of Molecular Biology and Genetics and Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
Milena Vuica
Stephen Desiderio
Howard Hughes Medical Institute · USJohns Hopkins University · US

Funding

TRANSPOSITION OF TN7P01CA016519 · NCI · JOHNS HOPKINS UNIVERSITY · PI BOEKE, JEF D · 1985 to 2010
$21.4M
NCI NIH HHS CA 16519NCI NIH HHS P01 CA016519
6 · The paper itself

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.

Indexed as

Nuclear Localization Signals3T3 CellsActive Transport, Cell Nucleusalpha KaryopherinsAnimalsBinding SitesCell CycleCell DivisionCell LineCell NucleusDNADNA-Binding ProteinsDNA NucleotidyltransferasesG1 PhaseGenes, RAG-1Homeodomain Proteinsalpha KaryopherinsDNADNA-Binding ProteinsDNA NucleotidyltransferasesHomeodomain ProteinsKPNA1 protein, humanNuclear Localization SignalsNuclear ProteinsRAG-1 proteinRAG2 protein, humanRag2 protein, mouseVDJ RecombinasesV(D)J recombination activating protein 2

Identifiers

PMID12861017
PMCPMC165718
OpenAlexW2116338238

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.