| http://purl.uniprot.org/citations/30209133 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30209133 | http://www.w3.org/2000/01/rdf-schema#comment | "Vascular calcification (or mineralization) is a common complication of chronic kidney disease (CKD) and is closely associated with increased mortality and morbidity rates. We recently reported that activation of the activating transcription factor 4 (ATF4) pathway through the saturated fatty acid (SFA)-induced endoplasmic reticulum (ER) stress response plays a causative role in CKD-associated vascular calcification. Here, using mouse models of CKD, we 1) studied the contribution of the proapoptotic transcription factor CCAAT enhancer-binding protein homologous protein (CHOP) to CKD-dependent medial calcification, and 2) we identified an additional regulator of ER stress-mediated CHOP expression. Transgenic mice having smooth muscle cell (SMC)-specific CHOP expression developed severe vascular apoptosis and medial calcification under CKD. Screening of a protein kinase inhibitor library identified 16 compounds, including seven cyclin-dependent kinase (CDK) inhibitors, that significantly suppressed CHOP induction during ER stress. Moreover, selective CDK9 inhibitors and CRISPR/Cas9-mediated CDK9 reduction blocked SFA-mediated induction of CHOP expression, whereas inhibitors of other CDK isoforms did not. Cyclin T1 knockout inhibited SFA-mediated induction of CHOP and mineralization, whereas deletion of cyclin T2 and cyclin K promoted CHOP expression levels and mineralization. Of note, the CDK9-cyclin T1 complex directly phosphorylated and activated ATF4. These results demonstrate that the CDK9-cyclin T1 and CDK9-cyclin T2/K complexes have opposing roles in CHOP expression and CKD-induced vascular calcification. They further reveal that the CDK9-cyclin T1 complex mediates vascular calcification through CHOP induction and phosphorylation-mediated ATF4 activation."xsd:string |
| http://purl.uniprot.org/citations/30209133 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.ra118.004706"xsd:string |
| http://purl.uniprot.org/citations/30209133 | http://purl.uniprot.org/core/author | "Miyazaki M."xsd:string |
| http://purl.uniprot.org/citations/30209133 | http://purl.uniprot.org/core/author | "Zhao X."xsd:string |
| http://purl.uniprot.org/citations/30209133 | http://purl.uniprot.org/core/author | "Williams K."xsd:string |
| http://purl.uniprot.org/citations/30209133 | http://purl.uniprot.org/core/author | "Okamura K."xsd:string |
| http://purl.uniprot.org/citations/30209133 | http://purl.uniprot.org/core/author | "Kohno S."xsd:string |
| http://purl.uniprot.org/citations/30209133 | http://purl.uniprot.org/core/author | "Chick W.S."xsd:string |
| http://purl.uniprot.org/citations/30209133 | http://purl.uniprot.org/core/author | "Keenan A.L."xsd:string |
| http://purl.uniprot.org/citations/30209133 | http://purl.uniprot.org/core/author | "Miyazaki-Anzai S."xsd:string |
| http://purl.uniprot.org/citations/30209133 | http://purl.uniprot.org/core/author | "Shiozaki Y."xsd:string |
| http://purl.uniprot.org/citations/30209133 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/30209133 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/30209133 | http://purl.uniprot.org/core/pages | "17008-17020"xsd:string |
| http://purl.uniprot.org/citations/30209133 | http://purl.uniprot.org/core/title | "The CDK9-cyclin T1 complex mediates saturated fatty acid-induced vascular calcification by inducing expression of the transcription factor CHOP."xsd:string |
| http://purl.uniprot.org/citations/30209133 | http://purl.uniprot.org/core/volume | "293"xsd:string |
| http://purl.uniprot.org/citations/30209133 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/30209133 |
| http://purl.uniprot.org/citations/30209133 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/30209133 |
| http://purl.uniprot.org/uniprot/#_D3YX14-mappedCitation-30209133 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30209133 |
| http://purl.uniprot.org/uniprot/#_E9Q7A7-mappedCitation-30209133 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30209133 |
| http://purl.uniprot.org/uniprot/#_A0A2R8VHR8-mappedCitation-30209133 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30209133 |
| http://purl.uniprot.org/uniprot/#_B0R021-mappedCitation-30209133 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30209133 |
| http://purl.uniprot.org/uniprot/#_D6RGN3-mappedCitation-30209133 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30209133 |
| http://purl.uniprot.org/uniprot/#_D6RHP4-mappedCitation-30209133 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30209133 |