Transactivation of Gene Expression by Myc is Inhibited by Mutation at the Phosphorylation Sites Thr-58 and Ser-62

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1993 Apr 15

PMID 8386367

Citations 54

Authors

S Gupta

A Seth

R J Davis

Affiliations

Soon will be listed here.

Abstract

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.

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