A link between c-Myc-mediated transcriptional repression and neoplastic transformation

Linda A Lee, Christine Dolde, John Barrett, Chyi S. Wu, Chi V. Dang

Research output: Contribution to journalArticle

Abstract

Recent studies indicate that the transcription factor c-Myc contributes to oncogenesis by altering the expression of genes involved in cell proliferation, but its precise function in neoplasia remains ambiguous. The ability of c-Myc to bind the sequence CAC(G/A)TG and transactivate appears to be linked to its transforming activity; however, c-Myc also represses transcription in vitro through a pyrimidine-rich cis element termed the initiator (Inr). In transfection experiments using the adenoviral major late (adML) promoter, which contains two Myc binding sites and an Inr, we determined that c-Myc represses transcription through the initiator in vivo. This activity requires the dimerization domain and amino acids 106 to 143, which are located within the transactivation domain and are necessary for neoplastic transformation. We studied a lymphoma-derived c-Myc substitution mutation at 115-Phe, which is within the region required for transcriptional suppression, and found the mutant more effective than wild-type c-Myc in transforming rodent fibroblasts and in suppressing the adML promoter. Our studies of both loss-of-function and gain-of-function c-Myc mutations suggest a link between c-Myc-mediated neoplastic transformation and transcriptional repression through the Inr.

Original languageEnglish (US)
Pages (from-to)1687-1695
Number of pages9
JournalJournal of Clinical Investigation
Volume97
Issue number7
StatePublished - Apr 1 1996

Fingerprint

Mutation
Dimerization
Transcriptional Activation
Transfection
Rodentia
Lymphoma
Carcinogenesis
Transcription Factors
Fibroblasts
Binding Sites
Cell Proliferation
Gene Expression
Amino Acids
Neoplasms
In Vitro Techniques
pyrimidine

Keywords

  • basic-helix-loop-helix
  • bHLH
  • Burkitt lymphoma
  • transrepression

ASJC Scopus subject areas

  • Medicine(all)

Cite this

A link between c-Myc-mediated transcriptional repression and neoplastic transformation. / Lee, Linda A; Dolde, Christine; Barrett, John; Wu, Chyi S.; Dang, Chi V.

In: Journal of Clinical Investigation, Vol. 97, No. 7, 01.04.1996, p. 1687-1695.

Research output: Contribution to journalArticle

Lee, LA, Dolde, C, Barrett, J, Wu, CS & Dang, CV 1996, 'A link between c-Myc-mediated transcriptional repression and neoplastic transformation', Journal of Clinical Investigation, vol. 97, no. 7, pp. 1687-1695.
Lee, Linda A ; Dolde, Christine ; Barrett, John ; Wu, Chyi S. ; Dang, Chi V. / A link between c-Myc-mediated transcriptional repression and neoplastic transformation. In: Journal of Clinical Investigation. 1996 ; Vol. 97, No. 7. pp. 1687-1695.
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