| http://purl.uniprot.org/citations/31462704 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31462704 | http://www.w3.org/2000/01/rdf-schema#comment | "Somatic missense mutations of the CSNK1A1 gene encoding casein kinase 1 alpha (CK1α) occur in a subset of myelodysplastic syndrome (MDS) with del(5q) karyotype. The chromosomal deletion causes CSNK1A1 haplo-insufficiency. CK1α mutations have also been observed in a variety of solid and hematopoietic tumors at low frequency. The functional consequence of CK1α mutation remains unknown. Here we show that tumor-associated CK1α mutations exclusively localize to the substrate-binding cleft. Functional analysis of recurrent mutants E98K and D140A revealed enhanced binding to the p53 inhibitor MDMX, increased ability to stimulate MDMX-p53 binding, and increased suppression of p21 expression. Furthermore, E98K and D140A mutants have reduced ability to promote phosphorylation of β-catenin, resulting in enhanced Wnt signaling. The results suggest that the CK1α mutations observed in tumors cause gain-of-function in cooperating with MDMX and inhibiting p53, and partial loss-of-function in suppressing Wnt signaling. These functional changes may promote expansion of abnormal myeloid progenitors in del(5q) MDS, and in rare cases drive the progression of other tumors."xsd:string |
| http://purl.uniprot.org/citations/31462704 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41388-019-0979-z"xsd:string |
| http://purl.uniprot.org/citations/31462704 | http://purl.uniprot.org/core/author | "Chen J."xsd:string |
| http://purl.uniprot.org/citations/31462704 | http://purl.uniprot.org/core/author | "Chen L."xsd:string |
| http://purl.uniprot.org/citations/31462704 | http://purl.uniprot.org/core/author | "Huang Q."xsd:string |
| http://purl.uniprot.org/citations/31462704 | http://purl.uniprot.org/core/author | "Liu X."xsd:string |
| http://purl.uniprot.org/citations/31462704 | http://purl.uniprot.org/core/author | "Zhang H."xsd:string |
| http://purl.uniprot.org/citations/31462704 | http://purl.uniprot.org/core/author | "Schonbrunn E."xsd:string |
| http://purl.uniprot.org/citations/31462704 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/31462704 | http://purl.uniprot.org/core/name | "Oncogene"xsd:string |
| http://purl.uniprot.org/citations/31462704 | http://purl.uniprot.org/core/pages | "176-186"xsd:string |
| http://purl.uniprot.org/citations/31462704 | http://purl.uniprot.org/core/title | "Tumor-derived CK1alpha mutations enhance MDMX inhibition of p53."xsd:string |
| http://purl.uniprot.org/citations/31462704 | http://purl.uniprot.org/core/volume | "39"xsd:string |
| http://purl.uniprot.org/citations/31462704 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/31462704 |
| http://purl.uniprot.org/citations/31462704 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/31462704 |
| http://purl.uniprot.org/uniprot/#_A0A087WTR9-mappedCitation-31462704 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31462704 |
| http://purl.uniprot.org/uniprot/#_A0A087WUE3-mappedCitation-31462704 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31462704 |
| http://purl.uniprot.org/uniprot/#_A0A0A0U7X4-mappedCitation-31462704 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31462704 |
| http://purl.uniprot.org/uniprot/#_A0A0M4B4Y9-mappedCitation-31462704 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31462704 |
| http://purl.uniprot.org/uniprot/#_A0A087WXZ1-mappedCitation-31462704 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31462704 |
| http://purl.uniprot.org/uniprot/#_A0A087WZ58-mappedCitation-31462704 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31462704 |
| http://purl.uniprot.org/uniprot/#_A0A0C4KX50-mappedCitation-31462704 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31462704 |
| http://purl.uniprot.org/uniprot/#_A0A0C4L134-mappedCitation-31462704 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31462704 |
| http://purl.uniprot.org/uniprot/#_A0A087X1Q1-mappedCitation-31462704 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31462704 |