| http://purl.uniprot.org/citations/27002159 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27002159 | http://www.w3.org/2000/01/rdf-schema#comment | "Activated α2-macroglobulin (α2M*) signals predominantly through cell surface GRP78 (CS-GRP78) to promote proliferation and survival of cancer cells; however, the molecular mechanism remains obscure. c-MYC is an essential transcriptional regulator that controls cell proliferation. We hypothesize that α2M*/CS-GRP78-evoked key signaling events are required for transcriptional activation of c-MYC target genes. Activation of CS-GRP78 by α2M* requires ligation of the GRP78 primary amino acid sequence (Leu(98)-Leu(115)). After stimulation with α2M*, CS-GRP78 signaling activates 3-phosphoinositide-dependent protein kinase-1 (PDK1) to induce phosphorylation of PLK1, which in turn induces c-MYC transcription. We demonstrate that PLK1 binds directly to c-MYC and promotes its transcriptional activity by phosphorylating Ser(62) Moreover, activated c-MYC is recruited to the E-boxes of target genes FOSL1 and ID2 by phosphorylating histone H3 at Ser(10) In addition, targeting the carboxyl-terminal domain of CS-GRP78 with a mAb suppresses transcriptional activation of c-MYC target genes and impairs cell proliferation. This work demonstrates that α2M*/CS-GRP78 acts as an upstream regulator of the PDK1/PLK1 signaling axis to modulate c-MYC transcription and its target genes, suggesting a therapeutic strategy for targeting c-MYC-associated malignant progression."xsd:string |
| http://purl.uniprot.org/citations/27002159 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m115.708131"xsd:string |
| http://purl.uniprot.org/citations/27002159 | http://purl.uniprot.org/core/author | "Pizzo S.V."xsd:string |
| http://purl.uniprot.org/citations/27002159 | http://purl.uniprot.org/core/author | "Gonzalez-Gronow M."xsd:string |
| http://purl.uniprot.org/citations/27002159 | http://purl.uniprot.org/core/author | "Gopal U."xsd:string |
| http://purl.uniprot.org/citations/27002159 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/27002159 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/27002159 | http://purl.uniprot.org/core/pages | "10904-10915"xsd:string |
| http://purl.uniprot.org/citations/27002159 | http://purl.uniprot.org/core/title | "Activated alpha2-Macroglobulin Regulates Transcriptional Activation of c-MYC Target Genes through Cell Surface GRP78 Protein."xsd:string |
| http://purl.uniprot.org/citations/27002159 | http://purl.uniprot.org/core/volume | "291"xsd:string |
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