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PMID: 8601634 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of clinical investigation ·Vol. 97 ·No. 7 ·1996-04-01 ·Pages 1687-95

Lee LA, Dolde C, Barrett J, Wu CS, Dang CV

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.

MeSH Terms
Animals Base Sequence Binding Sites/genetics Cell Line Cell Transformation, Neoplastic/genetics DNA Primers/genetics Genes, myc Humans L Cells Lymphoma/genetics Mice Molecular Sequence Data Mutation Plasmids/genetics Promoter Regions, Genetic Rats Transcription, Genetic Transfection
Chemicals
DNA Primers
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Lee L A
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA.
Dolde C
Barrett J
Wu C S
Dang C V
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI118595
Published
1996-04-01
Pages
1687-95
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC507233
Subset
IM
Grants
NCI NIH HHS · CA-51497 · United States
NCI NIH HHS · CA-57341 · United States
External Links
PubMed source DOI: 10.1172/JCI118595 PMC Full Text View journal details
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