A phosphorylation site located in the NH2-terminal domain of c-Myc increases transactivation of gene expression.
The c-myc gene encodes a sequence-specific DNA-binding protein (c-Myc) that forms leucine zipper complexes and can act as a transcription factor. Growth factor stimulation of cells causes the phosphorylation of the c-Myc transcriptional activation domain at Ser62 within a proline-rich region that is highly conserved among members of the Myc family (Alvarez, E., Northwood, I.C., Gonzalez, F. A., Latour, D. A., Seth, A., Abate, C., Curran, T., and Davis, R. J. (1991) J. Biol. Chem. 266, 15277-15285). This phosphorylation site is a substrate for growth factor-regulated MAP kinases and for the cell cycle-dependent protein kinase p34cdc2. We report that serum treatment of cells results in a marked increase in the transactivation of gene expression mediated by the c-Myc transcriptional activation domain. A point mutation at the site of growth factor-stimulated phosphorylation (Ser62) decreases the serum induction of transactivation. These data indicate that the c-Myc transcriptional activation domain may be a direct target of signal transduction pathways.
Seth
A
A
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester 01605.
Alvarez
E
E
Gupta
S
S
Davis
R J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D015870:Gene Expression; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D016254:Mutagenesis, Insertional; D010766:Phosphorylation; D010957:Plasmids; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D016271:Proto-Oncogene Proteins c-myc; D015500:Chloramphenicol O-Acetyltransferase