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

Hann SR, Dixit M, Sears RC, Sealy L
Genes Dev. 1994 8 (20): 2441-52

PMID: 7958908 · DOI:10.1101/gad.8.20.2441

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.

MeSH Terms (24)

Amino Acid Sequence Animals Avian Sarcoma Viruses Base Sequence Basic-Leucine Zipper Transcription Factors Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Binding Sites Cell Division Cell Line DNA DNA-Binding Proteins Enhancer Elements, Genetic HeLa Cells Humans Mice Molecular Sequence Data Mutagenesis, Site-Directed Peptide Chain Initiation, Translational Protein Biosynthesis Proto-Oncogene Proteins c-myc Repetitive Sequences, Nucleic Acid Transcription, Genetic Transcriptional Activation Transcription Factors

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