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• W1963016133 endingPage "5522" @default.
• W1963016133 startingPage "5510" @default.
• W1963016133 abstract "The N-terminal domain of the c-Myc protein has been reported to be critical for both the transactivation and biological functions of the c-Myc proteins. Through detailed phosphopeptide mapping analyses, we demonstrate that there is a cluster of four regulated and complex phosphorylation events on the N-terminal domain of Myc proteins, including Thr-58, Ser-62, and Ser-71. An apparent enhancement of Ser-62 phosphorylation occurs on v-Myc proteins having a mutation at Thr-58 which has previously been correlated with increased transforming ability. In contrast, phosphorylation of Thr-58 in cells is dependent on a prior phosphorylation of Ser-62. Hierarchical phosphorylation of c-Myc is also observed in vitro with a specific glycogen synthase kinase 3 alpha, unlike the promiscuous phosphorylation observed with other glycogen synthase kinase 3 alpha and 3 beta preparations. Although both p42 mitogen-activated protein kinase and cdc2 kinase specifically phosphorylate Ser-62 in vitro and cellular phosphorylation of Thr-58/Ser-62 is stimulated by mitogens, other in vivo experiments do not support a role for these kinases in the phosphorylation of Myc proteins. Unexpectedly, both the Thr-58 and Ser-62 phosphorylation events, but not other N-terminal phosphorylation events, can occur in the cytoplasm, suggesting that translocation of the c-Myc proteins to the nucleus is not required for phosphorylation at these sites. In addition, there appears to be an unusual block to the phosphorylation of Ser-62 during mitosis. Finally, although the enhanced transforming properties of Myc proteins correlates with the loss of phosphorylation at Thr-58 and an enhancement of Ser-62 phosphorylation, these phosphorylation events do not alter the ability of c-Myc to transactivate through the CACGTG Myc/Max binding site." @default.
• W1963016133 created "2016-06-24" @default.
• W1963016133 creator A5015735297 @default.
• W1963016133 creator A5025891672 @default.
• W1963016133 date "1994-08-01" @default.
• W1963016133 modified "2023-10-15" @default.
• W1963016133 title "Hierarchical phosphorylation at N-terminal transformation-sensitive sites in c-Myc protein is regulated by mitogens and in mitosis." @default.
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• W1963016133 doi "https://doi.org/10.1128/mcb.14.8.5510" @default.
• W1963016133 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/359071" @default.
• W1963016133 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/8035827" @default.
• W1963016133 hasPublicationYear "1994" @default.
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