ArticleMolecular and cellular biology1998
Loss of IkappaB alpha-mediated control over nuclear import and DNA binding enables oncogenic activation of c-Rel.
Article in Molecular and cellular biology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Adducin family proteins possess different nuclear export potentials.Journal of biomedical science · 2017Article
- Selective Inhibitor of Nuclear Export (SINE) Compounds Alter New World Alphavirus Capsid Localization and Reduce Viral Replication in Mammalian Cells.PLoS neglected tropical diseases · 2016Article
- David and Goliath: chemical perturbation of eukaryotes by bacteria.Journal of industrial microbiology & biotechnology · 2016Review
- Optogenetic control of nuclear protein export.Nature communications · 2016Article
- Peptidyl-prolyl isomerase Pin1 markedly enhances the oncogenic activity of the rel proteins in the nuclear factor-kappaB family.Cancer research · 2009Article
- The activation of TC10, a Rho small GTPase, contributes to v-Rel-mediated transformation.Oncogene · 2007Article
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- Interleukin-10 (IL-10) mediated suppression of IL-12 production in RAW 264.7 cells also involves c-rel transcription factor.Immunology · 2005Article
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- Regulation of c-Rel nuclear localization by binding of Ca2+/calmodulin.Molecular and cellular biology · 2003Article
- Differential regulation of the inhibitor of apoptosis ch-IAP1 by v-rel and the proto-oncogene c-rel.Journal of virology · 2002Article
- Cell stress and MEKK1-mediated c-Jun activation modulate NFkappaB activity and cell viability.Molecular biology of the cell · 2002Article
- Induction of apoptosis by TPA and VP-16 is through translocation of TR3.World journal of gastroenterology · 2002Article
- Mutational analysis of the v-Rel dimerization interface reveals a critical role for v-Rel homodimers in transformation.Journal of virology · 2002Article
- Postrepression activation of NF-kappaB requires the amino-terminal nuclear export signal specific to IkappaBalpha.Molecular and cellular biology · 2001Article
- Nuclear import of IkappaBalpha is accomplished by a ran-independent transport pathway.Molecular and cellular biology · 2000Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The IkappaB alpha protein is able both to inhibit nuclear import of Rel/NF-kappaB proteins and to mediate the export of Rel/NF-kappaB proteins from the nucleus. We now demonstrate that the c-Rel-IkappaB alpha complex is stably retained in the cytoplasm in the presence of leptomycin B, a specific inhibitor of Crm1-mediated nuclear export. In contrast, leptomycin B treatment results in the rapid and complete relocalization of the v-Rel-IkappaB alpha complex from the cytoplasm to the nucleus. IkappaB alpha also mediates the rapid nuclear shuttling of v-Rel in an interspecies heterokaryon assay. Thus, continuous nuclear export is required for cytoplasmic retention of the v-Rel-IkappaB alpha complex. Furthermore, although IkappaB alpha is able to mask the c-Rel-derived nuclear localization sequence (NLS), IkappaB alpha is unable to mask the v-Rel-derived NLS in the context of the v-Rel-IkappaB alpha complex. Taken together, our results demonstrate that IkappaB alpha is unable to inhibit nuclear import of v-Rel. We have identified two amino acid differences between c-Rel and v-Rel (Y286S and L302P) which link the failure of IkappaB alpha to inhibit nuclear import and DNA binding of a mutant c-Rel protein to oncogenesis. Our results support a model in which loss of IkappaB alpha-mediated control over c-Rel leads to oncogenic activation of c-Rel.
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Registered trials
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.