Transactivation of gene expression by Myc is inhibited by mutation at the phosphorylation sites Thr-58 and Ser-62
| Autor: | Alpna Seth, Shashi Gupta, Roger J. Davis |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Threonine
Transcriptional Activation Leucine zipper Molecular Sequence Data Genes myc Gene Expression Biology Polymerase Chain Reaction Cell Line Substrate Specificity Proto-Oncogene Proteins c-myc Gene product Transactivation Chlorocebus aethiops Gene expression Serine Animals Humans Point Mutation Amino Acid Sequence Phosphorylation Codon Site-directed mutagenesis Reporter gene Multidisciplinary Base Sequence DNA Molecular biology DNA binding site Oligodeoxyribonucleotides Calcium-Calmodulin-Dependent Protein Kinases Mutagenesis Site-Directed Protein Kinases Plasmids Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 90:3216-3220 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.90.8.3216 |
| Popis: | The product of the human c-myc protooncogene (Myc) is a sequence-specific DNA binding protein. Here, we demonstrate that the placement of the specific Myc DNA binding site CACGTG upstream of a luciferase reporter gene conferred Myc-stimulated expression that was inhibited by the overexpression of the basic-helix-loop-helix/leucine zipper protein Max. It was observed that Myc was phosphorylated in vivo within the NH2-terminal domain at Thr-58 and Ser-62. Replacement of these phosphorylation sites with Ala residues caused a marked decrease in Myc-stimulated reporter gene expression. In contrast, the replacement of Thr-58 or Ser-62 with an acidic residue (Glu) caused only a small inhibition of transactivation. Together, these data demonstrate that the NH2-terminal phosphorylation sites Thr-58 and Ser-62 are required for high levels of transactivation of gene expression by Myc. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|