Pain Repression Pathway

Preferred Label : Pain Repression Pathway;

NCIt related terms : Repression of Pain Sensation by the Transcriptional Regulator DREAM;

Alternative definition : BIOCARTA: The molecular events that lead to the perception of pain are a key research field in medicine and drug discovery. The opioid receptors modulate pain signaling in response to endogenous peptide ligands and opiate drugs such as morphine. The kappa opioid receptor plays a key role in the profound analgesia of opiates and is activated by the endogenous peptide ligand dynorphin, encoded by the prodynorphin gene. Production of prodynorphin is transcriptionally regulated by a downstream regulatory element (DRE) in the prodynorphin gene. A transcription factor called DREAM (DRE antagonistic modulator) binds to the DRE and represses prodynorphin transcription when bound. DREAM binds calcium with 4 EF-hand motifs and the binding of DREAM to DNA is repressed in the presence of calcium. Many transcription factors are regulated by calcium indirectly through calcium sensitive kinases and phosphatases, but DREAM is unique to date in being a transcription factor that directly binds calcium and is regulated by calcium binding. DREAM may also regulate other genes such as c-fos. DREAM is expressed in spinal cord neurons in regions involved in pain signaling. The regulation of prodynorphin expression by DREAM also leads to the hypothesis that DREAM is involved in pain signaling. Transgenic mice lacking the DREAM gene were unusually pain insensitive and had elevated spinal levels of dynorphin and tonic activation of the kappa opioid receptor, supporting this hypothesis. Other functions of DREAM may exist such as regulation of presenilins and potassium channel activity in the heart. DREAM is also known as calsenilin and KChIP3 through its association with these other proteins. These processes were not affected in mice lacking the DREAM gene however. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_dreampathway;

Details

Origin ID

C39052;

UMLS CUI

C1518855;

Semantic type(s)
- Molecular Function [UMLS semantic type]
has_gene_product_element
- Cyclic AMP-Responsive Element-Binding Protein 1 [NCIt concept]
- DNA-Directed RNA Polymerase II Subunit RPB1 [NCIt concept]
- Mitogen-Activated Protein Kinase 3 [NCIt concept]
- Proto-Oncogene c-Fos [NCIt concept]
- Transcription Factor AP-1 [NCIt concept]
- cAMP-Dependent Protein Kinase Catalytic Subunit Beta [NCIt concept]
- cAMP-Dependent Protein Kinase Catalytic Subunit Gamma [NCIt concept]
- cAMP-Dependent Protein Kinase Type I-Alpha Regulatory Subunit [NCIt concept]
- cAMP-Dependent Protein Kinase Type II-Alpha Regulatory Subunit [NCIt concept]
- cAMP-Responsive Element Modulator [NCIt concept]
pathway_has_gene_element
- CREB1 wt Allele [NCIt concept]
- CREM wt Allele [NCIt concept]
- FOS wt Allele [NCIt concept]
- JUN wt Allele [NCIt concept]
- MAPK3 wt Allele [NCIt concept]
- POLR2A wt Allele [NCIt concept]
- PRKACB wt Allele [NCIt concept]
- PRKACG wt Allele [NCIt concept]
- PRKAR1A wt Allele [NCIt concept]
- PRKAR2A wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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