The alternatively initiated c-Myc proteins differentially regulate transcription through a noncanonical DNA-binding site

Stephen R. Hann, Mrinalini Dixit, Rosalie C. Sears, Linda Sealy

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

The myc proto-oncogene family has been implicated in multiple cellular processes, including proliferation, differentiation, and apoptosis. The Myc proteins, as heterodimers with Max protein, have been shown to function as activators of transcription through an E-box DNA-binding element, CACGTG. We have now found that the c-Myc proteins regulate transcription through another, noncanonical, DNA sequence. The non-AUG-initiated form of the c-Myc protein, c-Myc 1, strongly and specifically activates transcription of the C/EBP sequences within the EFII enhancer element of the Rous sarcoma virus long terminal repeat. In contrast, comparable amounts of the AUG-initiated form, c-Myc 2, fail to significantly affect enhancer activity. However, both c-Myc proteins trans-activate the CACGTG sequence comparably. In addition, Myc/Max heterodimers, but not Max homodimers, bind to the EFII enhancer sequence in vitro. Finally, c-Myc 1 overexpression, but not c-Myc 2 overexpression, significantly inhibits cell growth. These results reveal new transcriptional activities for the Myc proteins and demonstrate that the different forms of the Myc protein are functionally distinct. These results also suggest an interplay between two different growth regulatory transcription factor families.

Original languageEnglish (US)
Pages (from-to)2441-2452
Number of pages12
JournalGenes and Development
Volume8
Issue number20
DOIs
StatePublished - Oct 15 1994

Keywords

  • C/EBP
  • c-myc
  • growth inhibition
  • non-AUG initiation
  • trans-activation

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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