| http://purl.uniprot.org/citations/10655479 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/10655479 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/10655479 | http://www.w3.org/2000/01/rdf-schema#comment | "Ligand-dependent down-regulation that leads to rapid and extensive loss of protein is characteristic of several nuclear steroid receptors, including human progesterone receptors (PRs). In breast cancer cells, >95% of PRs are degraded 6 h after the start of progestin treatment. The mechanism for down-regulation is unknown. We examined the role of PR phosphorylation by mitogen-activated protein kinases (MAPKs) in this process. Lactacystin and calpain inhibitor I, specific inhibitors of the 26S proteasome, blocked progestin-induced down-regulation, and ubiquitinated conjugates of PR accumulated in cells. Ligand-dependent PR degradation was also blocked by specific inhibition of p42 and p44 MAPKs. To define the targets of phosphorylation by this kinase, two serine/proline MAPK consensus sites on PR were mutated. We demonstrate that mutation of PR serine-294 to alanine (S294A) specifically and completely prevents ligand-dependent receptor down-regulation. We also find that rapid, ligand-independent degradation of immature PR intermediates occurs by a proteasome-mediated pathway. These results demonstrate that PR destruction, by either of two alternate routes, is mediated by the 26S proteasome. Specifically, down-regulation of mature PRs occurs by a mechanism in which ligand binding activates PR phosphorylation by MAPKs at a unique serine residue, which then targets the receptors for degradation."xsd:string |
| http://purl.uniprot.org/citations/10655479 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.97.3.1032"xsd:string |
| http://purl.uniprot.org/citations/10655479 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.97.3.1032"xsd:string |
| http://purl.uniprot.org/citations/10655479 | http://purl.uniprot.org/core/author | "Shen T."xsd:string |
| http://purl.uniprot.org/citations/10655479 | http://purl.uniprot.org/core/author | "Shen T."xsd:string |
| http://purl.uniprot.org/citations/10655479 | http://purl.uniprot.org/core/author | "Horwitz K.B."xsd:string |
| http://purl.uniprot.org/citations/10655479 | http://purl.uniprot.org/core/author | "Horwitz K.B."xsd:string |
| http://purl.uniprot.org/citations/10655479 | http://purl.uniprot.org/core/author | "Lange C.A."xsd:string |
| http://purl.uniprot.org/citations/10655479 | http://purl.uniprot.org/core/author | "Lange C.A."xsd:string |
| http://purl.uniprot.org/citations/10655479 | http://purl.uniprot.org/core/date | "2000"xsd:gYear |
| http://purl.uniprot.org/citations/10655479 | http://purl.uniprot.org/core/date | "2000"xsd:gYear |
| http://purl.uniprot.org/citations/10655479 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |
| http://purl.uniprot.org/citations/10655479 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |
| http://purl.uniprot.org/citations/10655479 | http://purl.uniprot.org/core/pages | "1032-1037"xsd:string |
| http://purl.uniprot.org/citations/10655479 | http://purl.uniprot.org/core/pages | "1032-1037"xsd:string |
| http://purl.uniprot.org/citations/10655479 | http://purl.uniprot.org/core/title | "Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26S proteasome."xsd:string |
| http://purl.uniprot.org/citations/10655479 | http://purl.uniprot.org/core/title | "Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26S proteasome."xsd:string |
| http://purl.uniprot.org/citations/10655479 | http://purl.uniprot.org/core/volume | "97"xsd:string |
| http://purl.uniprot.org/citations/10655479 | http://purl.uniprot.org/core/volume | "97"xsd:string |
| http://purl.uniprot.org/citations/10655479 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/10655479 |
| http://purl.uniprot.org/citations/10655479 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/10655479 |
| http://purl.uniprot.org/citations/10655479 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/10655479 |
| http://purl.uniprot.org/citations/10655479 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/10655479 |