Sr. Hann et al., THE ALTERNATIVELY INITIATED C-MYC PROTEINS DIFFERENTIALLY REGULATE TRANSCRIPTION THROUGH A NONCANONICAL DNA-BINDING SITE, Genes & development, 8(20), 1994, pp. 2441-2452
The myc proto-oncogene family has been implicated in multiple cellular
processes, including proliferation, differentiation, and apoptosis. T
he Myc proteins, as heterodimers with Max protein, have been shown to
function as activators of transcription through an E-box DNA-binding e
lement, CACGTG. We have now found that the c-Myc proteins regulate tra
nscription through another, noncanonical, DNA sequence. The non-AUG in
itiated form of the c-Myc protein, c-Myc 1, strongly and specifically
activates transcription of the C/EBP sequences within the EFII enhance
r element of the Rous sarcoma virus long terminal repeat. In contrast,
comparable amounts of the AUG-initiated form, c-Myc 2, fail to signif
icantly affect enhancer activity. However, both c-Myc proteins trans-a
ctivate the CACGTG sequence comparably. In addition, Myc/Max heterodim
ers, but not Max homodimers, bind to the EFII enhancer sequence in vit
ro. finally, c-Myc 1 overexpression, but not c-Myc 2 overexpression, s
ignificantly inhibits cell growth. These results reveal new transcript
ional activities for the Myc proteins and demonstrate that the differe
nt farms of the Myc protein are functionally distinct. These results a
lso suggest an interplay between two different growth regulatory trans
cription factor families.