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Publication : The neogenin intracellular domain regulates gene transcription via nuclear translocation.

First Author  Goldschneider D Year  2008
Journal  Mol Cell Biol Volume  28
Issue  12 Pages  4068-79
PubMed ID  18391016 Mgi Jnum  J:137319
Mgi Id  MGI:3798755 Doi  10.1128/MCB.02114-07
Citation  Goldschneider D, et al. (2008) The neogenin intracellular domain regulates gene transcription via nuclear translocation. Mol Cell Biol 28(12):4068-79
abstractText  Neogenin is a multifunctional receptor implicated in axon navigation, neuronal differentiation, morphogenesis, and cell death. Very little is known about signaling downstream of neogenin. Because we found that the neogenin intracellular domain (NeICD) interacts with nuclear proteins implicated in transcription regulation, we investigated further whether neogenin signals similarly to the Notch receptor. We show here that neogenin is cleaved by gamma-secretase, an event that releases the complete NeICD. We also describe that NeICD is located at the nucleus, a feature regulated through a balance between nuclear import and export. NeICD triggers gene reporter transactivation and associates with nuclear chromatin. Direct transcriptional targets of NeICD were determined and were shown to be up-regulated in the presence of neogenin ligand. Together, we reveal here a novel aspect of neogenin signaling that relies on the direct implication of its intracellular domain in transcriptional regulation.
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