| http://purl.uniprot.org/citations/32024692 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32024692 | http://www.w3.org/2000/01/rdf-schema#comment | "NF-κB is a pro-inflammatory transcription factor that critically regulates immune responses and other distinct cellular pathways. However, many NF-κB-mediated pathways for cell survival and apoptosis signaling in cancer remain to be elucidated. Cell cycle and apoptosis regulatory protein 1 (CARP-1 or CCAR1) is a perinuclear phosphoprotein that regulates signaling induced by anticancer chemotherapy and growth factors. Although previous studies have reported that CARP-1 is a part of the NF-κB proteome, regulation of NF-κB signaling by CARP-1 and the molecular mechanism(s) involved are unclear. Here, we report that CARP-1 directly binds the NF-κB-activating kinase IκB kinase subunit γ (NEMO or NF-κB essential modulator) and regulates the chemotherapy-activated canonical NF-κB pathway. Importantly, blockade of NEMO-CARP-1 binding diminished NF-κB activation, indicated by reduced phosphorylation of its subunit p65/RelA by the chemotherapeutic agent adriamycin (ADR), but not NF-κB activation induced by tumor necrosis factor α (TNFα), interleukin (IL)-1β, or epidermal growth factor. High-throughput screening of a chemical library yielded a small molecule inhibitor of NEMO-CARP-1 binding, termed selective NF-κB inhibitor 1 (SNI)-1). We noted that SNI-1 enhances chemotherapy-dependent growth inhibition of a variety of cancer cells, including human triple-negative breast cancer (TNBC) and patient-derived TNBC cells in vitro, and attenuates chemotherapy-induced secretion of the pro-inflammatory cytokines TNFα, IL-1β, and IL-8. SNI-1 also enhanced ADR or cisplatin inhibition of murine TNBC tumors in vivo and reduced systemic levels of pro-inflammatory cytokines. We conclude that inhibition of NEMO-CARP-1 binding enhances responses of cancer cells to chemotherapy."xsd:string |
| http://purl.uniprot.org/citations/32024692 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.ra119.009898"xsd:string |
| http://purl.uniprot.org/citations/32024692 | http://purl.uniprot.org/core/author | "Rishi A.K."xsd:string |
| http://purl.uniprot.org/citations/32024692 | http://purl.uniprot.org/core/author | "Venkatesh J."xsd:string |
| http://purl.uniprot.org/citations/32024692 | http://purl.uniprot.org/core/author | "Meister P."xsd:string |
| http://purl.uniprot.org/citations/32024692 | http://purl.uniprot.org/core/author | "Cheriyan V.T."xsd:string |
| http://purl.uniprot.org/citations/32024692 | http://purl.uniprot.org/core/author | "Muthu M."xsd:string |
| http://purl.uniprot.org/citations/32024692 | http://purl.uniprot.org/core/author | "Levi E."xsd:string |
| http://purl.uniprot.org/citations/32024692 | http://purl.uniprot.org/core/author | "Dzinic S."xsd:string |
| http://purl.uniprot.org/citations/32024692 | http://purl.uniprot.org/core/author | "Sekhar S.C."xsd:string |
| http://purl.uniprot.org/citations/32024692 | http://purl.uniprot.org/core/author | "Polin L.A."xsd:string |
| http://purl.uniprot.org/citations/32024692 | http://purl.uniprot.org/core/author | "Gauld J.W."xsd:string |
| http://purl.uniprot.org/citations/32024692 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32024692 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/32024692 | http://purl.uniprot.org/core/pages | "3532-3552"xsd:string |
| http://purl.uniprot.org/citations/32024692 | http://purl.uniprot.org/core/title | "Antagonizing binding of cell cycle and apoptosis regulatory protein 1 (CARP-1) to the NEMO/IKKgamma protein enhances the anticancer effect of chemotherapy."xsd:string |
| http://purl.uniprot.org/citations/32024692 | http://purl.uniprot.org/core/volume | "295"xsd:string |
| http://purl.uniprot.org/citations/32024692 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32024692 |
| http://purl.uniprot.org/citations/32024692 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/32024692 |
| http://purl.uniprot.org/uniprot/#_A0A0C4DGG8-mappedCitation-32024692 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32024692 |
| http://purl.uniprot.org/uniprot/#_A0A087X1B1-mappedCitation-32024692 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32024692 |
| http://purl.uniprot.org/uniprot/#_D3DWY0-mappedCitation-32024692 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32024692 |
| http://purl.uniprot.org/uniprot/#_Q8IX12-mappedCitation-32024692 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32024692 |
| http://purl.uniprot.org/uniprot/#_Q9Y6K9-mappedCitation-32024692 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32024692 |