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- W2100027477 abstract "ABSTRACT The NGFI-B (Nur77) subfamily of orphan nuclear receptors (NRs), which also includes Nurr1 and NOR1, bind the NurRE regulatory element as either homo- or heterodimers formed between subfamily members. These NRs mediate the activation of pituitary proopiomelanocortin (POMC) gene transcription by the hypothalamic hormone corticotropin-releasing hormone (CRH), an important link between neuronal and endocrine components of the hypothalamo-pituitary-adrenal axis. CRH effects on POMC transcription do not require de novo protein synthesis. We now show that CRH signals activate Nur factors through the cyclic AMP/protein kinase A (PKA) pathway. CRH and PKA rapidly increase nuclear DNA binding activity of NGFI-B dimers but not monomers. Accordingly, CRH- or PKA-activated Nur factors enhance dimer (but not monomer) target response elements. We also show that p160/SRC coactivators are recruited to Nur dimers (but not to monomers) and that coactivator recruitment to the NurRE is enhanced in response to CRH. Moreover, PKA- and coactivator-induced potentiation of NGFI-B activity are primarily exerted through the N-terminal AF-1 domain of NGFI-B. The TIF2 (SRC-2) glutamine-rich domain is required for this activity. Taken together, these results indicate that Nur factors behave as endpoint effectors of the PKA signaling pathway acting through dimers and AF-1-dependent recruitment of coactivators." @default.
- W2100027477 created "2016-06-24" @default.
- W2100027477 creator A5031203614 @default.
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- W2100027477 creator A5059647024 @default.
- W2100027477 creator A5059939017 @default.
- W2100027477 creator A5087707832 @default.
- W2100027477 date "2003-02-01" @default.
- W2100027477 modified "2023-10-16" @default.
- W2100027477 title "Dimer-Specific Potentiation of NGFI-B (Nur77) Transcriptional Activity by the Protein Kinase A Pathway and AF-1-Dependent Coactivator Recruitment" @default.
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- W2100027477 doi "https://doi.org/10.1128/mcb.23.3.763-776.2003" @default.
- W2100027477 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/140697" @default.
- W2100027477 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12529383" @default.
- W2100027477 hasPublicationYear "2003" @default.
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