| http://purl.uniprot.org/citations/35169254 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35169254 | http://www.w3.org/2000/01/rdf-schema#comment | "Hypoxia-inducible factor-1α (HIF-1α) plays central roles in the hypoxia response. It is highly expressed in multiple cancers, but not always correlated with hypoxia. Mutation of the von Hippel-Lindau (VHL) gene, which encodes an E3 ligase, contributes to the constructive activation of HIF-1α in specific tumor types, as exemplified by renal cell carcinoma; but how VHL wild-type tumors acquire this ability is not completely understood. Here, we found that the oncogene iASPP (inhibitor of apoptosis-simulating protein of p53) plays essential roles in such a context. Genetic inhibition of iASPP reduced tumor growth, accompanied by impaired angiogenesis, increased areas of tumor necrosis, and reduced glycolysis that was HIF-1α-dependent. These abilities of iASPP were validated by in vitro assays. Mechanistically, iASPP directly binds VHL at its β domain, a region also involved in HIF-1α binding, therefore blocking VHL's binding and the subsequent degradation of HIF-1α protein under normoxia. iASPP levels correlate with HIF-1α protein and vascular endothelial growth factor (VEGF) and the glucose transporter protein type 1(GLUT1), representative HIF-1α target genes, in human colon cancer tissues. Furthermore, inhibition of iASPP expression synergizes with low toxic dose of the HIF-1α inhibitor YC-1 to inhibit HIF-1α expression and tumor growth. Our findings suggest that iASPP contributes to HIF-1α activation in cancers, and that iASPP-mediated HIF-1α stabilization has potential as a therapeutic approach against cancer."xsd:string |
| http://purl.uniprot.org/citations/35169254 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41388-022-02234-9"xsd:string |
| http://purl.uniprot.org/citations/35169254 | http://purl.uniprot.org/core/author | "Hu Y."xsd:string |
| http://purl.uniprot.org/citations/35169254 | http://purl.uniprot.org/core/author | "Liu H."xsd:string |
| http://purl.uniprot.org/citations/35169254 | http://purl.uniprot.org/core/author | "Li L."xsd:string |
| http://purl.uniprot.org/citations/35169254 | http://purl.uniprot.org/core/author | "Wang X."xsd:string |
| http://purl.uniprot.org/citations/35169254 | http://purl.uniprot.org/core/author | "Zhao D."xsd:string |
| http://purl.uniprot.org/citations/35169254 | http://purl.uniprot.org/core/author | "Zhao K."xsd:string |
| http://purl.uniprot.org/citations/35169254 | http://purl.uniprot.org/core/author | "Zheng S."xsd:string |
| http://purl.uniprot.org/citations/35169254 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/35169254 | http://purl.uniprot.org/core/name | "Oncogene"xsd:string |
| http://purl.uniprot.org/citations/35169254 | http://purl.uniprot.org/core/pages | "1944-1958"xsd:string |
| http://purl.uniprot.org/citations/35169254 | http://purl.uniprot.org/core/title | "iASPP is essential for HIF-1alpha stabilization to promote angiogenesis and glycolysis via attenuating VHL-mediated protein degradation."xsd:string |
| http://purl.uniprot.org/citations/35169254 | http://purl.uniprot.org/core/volume | "41"xsd:string |
| http://purl.uniprot.org/citations/35169254 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/35169254 |
| http://purl.uniprot.org/citations/35169254 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/35169254 |
| http://purl.uniprot.org/uniprot/#_D0VY79-mappedCitation-35169254 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35169254 |
| http://purl.uniprot.org/uniprot/#_A0A024R2F2-mappedCitation-35169254 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35169254 |
| http://purl.uniprot.org/uniprot/#_A4ZYX2-mappedCitation-35169254 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35169254 |
| http://purl.uniprot.org/uniprot/#_A7YME7-mappedCitation-35169254 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35169254 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z4K1-mappedCitation-35169254 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35169254 |
| http://purl.uniprot.org/uniprot/#_B2R617-mappedCitation-35169254 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35169254 |
| http://purl.uniprot.org/uniprot/#_B4E1V7-mappedCitation-35169254 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35169254 |
| http://purl.uniprot.org/uniprot/#_A0PJF6-mappedCitation-35169254 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35169254 |