| http://purl.uniprot.org/citations/32034211 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32034211 | http://www.w3.org/2000/01/rdf-schema#comment | "Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a pleiotropic protein, promoting both tumor-suppressive and tumor-promoting activities. While TIMP-1 is primarily known as an endogenous inhibitor of matrix metalloproteinases (MMPs) and thus associated with tumor cell invasion, clinical studies demonstrated increased expression of TIMP-1 and its association with poor prognosis in cancer. Non-MMP-inhibitory and oncogenic functions of TIMP-1 are mediated by induction of intracellular signaling via its cell surface receptor CD63, a tetraspanin. The present study investigates the structure-function relationship of TIMP-1 for its interaction with CD63, which may eventually help design a novel approach for targeting TIMP-1's pro-oncogenic activity without interfering its tumor suppressive MMP-inhibitory function. Importantly, our analysis includes TIMP-1/CD63 interactions at the cell surface of live cells. Here, we demonstrate that the 9 C-terminal amino acid residues of TIMP-1 and the large extracellular loop of CD63 are required for their interaction. Considering that the N-terminal half of TIMP-1 is sufficient for TIMP-1's MMP-inhibitory activity, we propose that those C-terminal amino acid residues are a potentially targetable motif of TIMP-1 oncogenic activity. As a proof of concept, we present the potential for the development of neutralizing antibodies against the C-terminal motif of TIMP-1 for disruption of TIMP-1 interaction with CD63 and the subsequent signal transduction."xsd:string |
| http://purl.uniprot.org/citations/32034211 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41598-020-58964-x"xsd:string |
| http://purl.uniprot.org/citations/32034211 | http://purl.uniprot.org/core/author | "Kim S."xsd:string |
| http://purl.uniprot.org/citations/32034211 | http://purl.uniprot.org/core/author | "Najy A.J."xsd:string |
| http://purl.uniprot.org/citations/32034211 | http://purl.uniprot.org/core/author | "Jung Y.S."xsd:string |
| http://purl.uniprot.org/citations/32034211 | http://purl.uniprot.org/core/author | "Kim H.C."xsd:string |
| http://purl.uniprot.org/citations/32034211 | http://purl.uniprot.org/core/author | "Fridman R."xsd:string |
| http://purl.uniprot.org/citations/32034211 | http://purl.uniprot.org/core/author | "Warner R.B."xsd:string |
| http://purl.uniprot.org/citations/32034211 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32034211 | http://purl.uniprot.org/core/name | "Sci Rep"xsd:string |
| http://purl.uniprot.org/citations/32034211 | http://purl.uniprot.org/core/pages | "2099"xsd:string |
| http://purl.uniprot.org/citations/32034211 | http://purl.uniprot.org/core/title | "Establishment of Structure-Function Relationship of Tissue Inhibitor of Metalloproteinase-1 for Its Interaction with CD63: Implication for Cancer Therapy."xsd:string |
| http://purl.uniprot.org/citations/32034211 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/32034211 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32034211 |
| http://purl.uniprot.org/citations/32034211 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/32034211 |
| http://purl.uniprot.org/uniprot/#_B3KQF4-mappedCitation-32034211 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32034211 |
| http://purl.uniprot.org/uniprot/#_B4DJK3-mappedCitation-32034211 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32034211 |
| http://purl.uniprot.org/uniprot/#_P01033-mappedCitation-32034211 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32034211 |
| http://purl.uniprot.org/uniprot/#_Q6FGX5-mappedCitation-32034211 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32034211 |
| http://purl.uniprot.org/uniprot/#_Q58P21-mappedCitation-32034211 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32034211 |
| http://purl.uniprot.org/uniprot/B4DJK3 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/32034211 |
| http://purl.uniprot.org/uniprot/Q58P21 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/32034211 |
| http://purl.uniprot.org/uniprot/B3KQF4 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/32034211 |
| http://purl.uniprot.org/uniprot/P01033 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/32034211 |