| http://purl.uniprot.org/citations/17634226 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17634226 | http://www.w3.org/2000/01/rdf-schema#comment | "The Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) protein is functionally pleiotropic. LANA contributes to KSHV-associated pathogenesis, in part, by increasing entry of cells into S phase through a process that is driven by LANA interaction with the serine-threonine kinase glycogen synthase kinase 3 (GSK-3) and stabilization of beta-catenin. We now show that LANA affects the activity of another protein involved in cell cycle regulation, c-Myc. Sequencing of c-Myc coding sequences revealed that c-Myc in KSHV-positive primary effusion lymphoma (PEL) cell lines is wild type in the N-terminal region that regulates c-Myc protein stability. Despite this, c-Myc in PEL cells is stabilized. In LANA-expressing cells, inactivation of nuclear GSK-3 reduced phosphorylation of c-Myc at Thr58 and contributed to c-Myc stabilization by decreasing c-Myc ubiquitination. Phosphorylation of c-Myc on Ser62 also affects c-Myc stability and function. We now show that LANA increases the level of phosphorylated extracellular signal-regulated kinase 1 (ERK1) and increases ERK phosphorylation of c-Myc on Ser62. LANA also interacted with c-Myc, and c-Myc amino acids 147 to 220 were required for this interaction. LANA (L1006P) retained the ability to bind to c-Myc and activate ERK1, indicating that these events did not require LANA interaction with GSK-3. Thus, LANA stabilizes c-Myc; prevents the phosphorylation of c-Myc at Thr58, an event that promotes Myc-induced apoptosis; and independently stimulates phosphorylation of c-Myc at Ser62, an event that transcriptionally activates c-Myc. LANA-mediated manipulation of c-Myc function is likely to contribute to KSHV-associated tumorigenesis through the induction of c-Myc regulated cellular genes, as well as by the stimulation of cell cycle progression."xsd:string |
| http://purl.uniprot.org/citations/17634226 | http://purl.org/dc/terms/identifier | "doi:10.1128/jvi.00804-07"xsd:string |
| http://purl.uniprot.org/citations/17634226 | http://purl.uniprot.org/core/author | "Hayward S.D."xsd:string |
| http://purl.uniprot.org/citations/17634226 | http://purl.uniprot.org/core/author | "Liao G."xsd:string |
| http://purl.uniprot.org/citations/17634226 | http://purl.uniprot.org/core/author | "Liu J."xsd:string |
| http://purl.uniprot.org/citations/17634226 | http://purl.uniprot.org/core/author | "Martin H.J."xsd:string |
| http://purl.uniprot.org/citations/17634226 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17634226 | http://purl.uniprot.org/core/name | "J Virol"xsd:string |
| http://purl.uniprot.org/citations/17634226 | http://purl.uniprot.org/core/pages | "10451-10459"xsd:string |
| http://purl.uniprot.org/citations/17634226 | http://purl.uniprot.org/core/title | "The Kaposi's sarcoma-associated herpesvirus LANA protein stabilizes and activates c-Myc."xsd:string |
| http://purl.uniprot.org/citations/17634226 | http://purl.uniprot.org/core/volume | "81"xsd:string |
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