GSBS Student Publications


Transactivation of gene expression by Myc is inhibited by mutation at the phosphorylation sites Thr-58 and Ser-62

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Molecular Medicine



Document Type


Medical Subject Headings

Amino Acid Sequence; Animals; Base Sequence; Calcium-Calmodulin-Dependent Protein Kinases; Cell Line; Cercopithecus aethiops; Codon; DNA; Gene Expression; Genes, myc; Humans; Molecular Sequence Data; *Mutagenesis, Site-Directed; Oligodeoxyribonucleotides; Phosphorylation; Plasmids; Point Mutation; Polymerase Chain Reaction; Protein Kinases; Proto-Oncogene Proteins c-myc; *Serine; Substrate Specificity; *Threonine; *Trans-Activation (Genetics)


Life Sciences | Medicine and Health Sciences


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.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3216-20.

Related Resources

Link to article in PubMed

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID