| http://purl.uniprot.org/citations/17463001 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17463001 | http://www.w3.org/2000/01/rdf-schema#comment | "Mcl-1 is an antiapoptotic Bcl-2 family member that is highly regulated and when dysregulated contributes to cancer. The Mcl-1 protein is phosphorylated at multiple sites in response to different signaling events. Phosphorylations at Thr163 (by ERK) and Ser159 (by glycogen-synthase kinase 3beta) have recently been shown to slow and enhance, respectively, Mcl-1 protein turnover. Phosphorylation is also known to be stimulated at other, as-yet uncharacterized sites in the G2/M phase of the cell cycle. Using an S peptide-tagged Mcl-1 T163A mutant, Ser64 was identified as a novel Mcl-1 phosphorylation site by mass spectrometry. Immunoblotting demonstrated that phosphorylation at this site was maximal in cells in G2/M phase, was enhanced by tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) treatment, was blocked by inhibitors of CDK (but not ERK or glycogen-synthase kinase 3beta), and was stimulated in vitro by CDK 1, CDK2, and JNK1. The half-life of a nonphosphorylatable S64A Mcl-1 mutant was indistinguishable from that of the wild type polypeptide. In contrast, this mutant failed to protect cells from TRAIL-mediated apoptosis, whereas reconstitution with the phosphomimetic S64E Mcl-1 mutant rendered cells TRAIL-resistant. This anti-apoptotic phenotype of the S64E Mcl-1 mutant was also associated with enhanced binding to the proapoptotic proteins Bim, Noxa, and Bak. A pharmacological CDK inhibitor that reduced Ser64 phosphorylation also sensitized cells to TRAIL cytotoxicity. Collectively, these observations not only identify G2/M-associated phosphorylation at Ser64 as a critical determinant of the antiapoptotic activity of Mcl-1 but also elucidate a novel mechanism by which CDK1/2 inhibitors can enhance the effectiveness of the cytotoxic cytokine TRAIL."xsd:string |
| http://purl.uniprot.org/citations/17463001 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m610010200"xsd:string |
| http://purl.uniprot.org/citations/17463001 | http://purl.uniprot.org/core/author | "Lee S.H."xsd:string |
| http://purl.uniprot.org/citations/17463001 | http://purl.uniprot.org/core/author | "Kobayashi S."xsd:string |
| http://purl.uniprot.org/citations/17463001 | http://purl.uniprot.org/core/author | "Kaufmann S.H."xsd:string |
| http://purl.uniprot.org/citations/17463001 | http://purl.uniprot.org/core/author | "Meng X.W."xsd:string |
| http://purl.uniprot.org/citations/17463001 | http://purl.uniprot.org/core/author | "Mott J.L."xsd:string |
| http://purl.uniprot.org/citations/17463001 | http://purl.uniprot.org/core/author | "Craig R.W."xsd:string |
| http://purl.uniprot.org/citations/17463001 | http://purl.uniprot.org/core/author | "Gores G.J."xsd:string |
| http://purl.uniprot.org/citations/17463001 | http://purl.uniprot.org/core/author | "Bronk S.F."xsd:string |
| http://purl.uniprot.org/citations/17463001 | http://purl.uniprot.org/core/author | "Werneburg N.W."xsd:string |
| http://purl.uniprot.org/citations/17463001 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17463001 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/17463001 | http://purl.uniprot.org/core/pages | "18407-18417"xsd:string |
| http://purl.uniprot.org/citations/17463001 | http://purl.uniprot.org/core/title | "Serine 64 phosphorylation enhances the antiapoptotic function of Mcl-1."xsd:string |
| http://purl.uniprot.org/citations/17463001 | http://purl.uniprot.org/core/volume | "282"xsd:string |
| http://purl.uniprot.org/citations/17463001 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/17463001 |
| http://purl.uniprot.org/citations/17463001 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/17463001 |
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| http://purl.uniprot.org/uniprot/#_B4DLY8-mappedCitation-17463001 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17463001 |