C-myc transcriptional repression is linked to cell transformation

Linda A Lee, C. Dolde, C. S. Wu, J. Barrett, C. V. Dang

Research output: Contribution to journalArticle

Abstract

The c-Myc oncoprotein is a transcription factor known to participate in cell proliferation, apoptosis, and cell transformation. It is widely believed that c-Myc promotes oncogenesis by transactivating genes that regulate cell growth. Recently cMyc mediated repression of promoters containing an initiator element (Inr) has also been reported but its relevance to cell transformation remains unknown. The Inr is a pyrimidine-rich DNA sequence found in several TATA-less promoters of genes that are regulated during differentiation. We chose to delineate c-Myc transcriptional repression through the Inr in transient transfection assays using the adenoviral major late {adML) promoter which contains two Myc binding sites and an Inr. Methods/Results: We observed that c-Myc represses the adML promoter through the initiator element. To determine which functional domains of the c-Myc protein are necessary for transcriptional repression, we used Myc deletion mutants in similar experiments and found that amino acids 106-143 of the c-Myc transactivation domain and the dimerization motif are required for transcriptional repression. We then examined the transcription and transformation properties of a lymphoma-derived mutant, MycB2, that contains a mutation (115-Phe) within one region critical for repression. This mutant repressed transcription to a greater extent than wild-type cMyc. The mutant also conferred a greater cell growth potential than wild-type c-Myc in soft-anchorage independent growth and ras cotransformation assays. Conclusion: These findings link c-Myc transcriptional repression with cell transformation, thus posing an additional mechanism by which c-Myc could potentially transform cells.

Original languageEnglish (US)
JournalJournal of Investigative Medicine
Volume44
Issue number3
StatePublished - 1996

Fingerprint

Cell growth
Transcription
Assays
Genes
Proto-Oncogene Proteins c-myc
Dimerization
Oncogene Proteins
DNA sequences
Cell proliferation
Transcription Factors
Binding Sites
Apoptosis
Amino Acids
Growth
Experiments
Transcriptional Activation
Transfection
Lymphoma
Carcinogenesis
Cell Proliferation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

C-myc transcriptional repression is linked to cell transformation. / Lee, Linda A; Dolde, C.; Wu, C. S.; Barrett, J.; Dang, C. V.

In: Journal of Investigative Medicine, Vol. 44, No. 3, 1996.

Research output: Contribution to journalArticle

Lee, Linda A ; Dolde, C. ; Wu, C. S. ; Barrett, J. ; Dang, C. V. / C-myc transcriptional repression is linked to cell transformation. In: Journal of Investigative Medicine. 1996 ; Vol. 44, No. 3.
@article{29bc5795d3fb433bbb5fc76d070a408d,
title = "C-myc transcriptional repression is linked to cell transformation",
abstract = "The c-Myc oncoprotein is a transcription factor known to participate in cell proliferation, apoptosis, and cell transformation. It is widely believed that c-Myc promotes oncogenesis by transactivating genes that regulate cell growth. Recently cMyc mediated repression of promoters containing an initiator element (Inr) has also been reported but its relevance to cell transformation remains unknown. The Inr is a pyrimidine-rich DNA sequence found in several TATA-less promoters of genes that are regulated during differentiation. We chose to delineate c-Myc transcriptional repression through the Inr in transient transfection assays using the adenoviral major late {adML) promoter which contains two Myc binding sites and an Inr. Methods/Results: We observed that c-Myc represses the adML promoter through the initiator element. To determine which functional domains of the c-Myc protein are necessary for transcriptional repression, we used Myc deletion mutants in similar experiments and found that amino acids 106-143 of the c-Myc transactivation domain and the dimerization motif are required for transcriptional repression. We then examined the transcription and transformation properties of a lymphoma-derived mutant, MycB2, that contains a mutation (115-Phe) within one region critical for repression. This mutant repressed transcription to a greater extent than wild-type cMyc. The mutant also conferred a greater cell growth potential than wild-type c-Myc in soft-anchorage independent growth and ras cotransformation assays. Conclusion: These findings link c-Myc transcriptional repression with cell transformation, thus posing an additional mechanism by which c-Myc could potentially transform cells.",
author = "Lee, {Linda A} and C. Dolde and Wu, {C. S.} and J. Barrett and Dang, {C. V.}",
year = "1996",
language = "English (US)",
volume = "44",
journal = "Journal of Investigative Medicine",
issn = "1081-5589",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - C-myc transcriptional repression is linked to cell transformation

AU - Lee, Linda A

AU - Dolde, C.

AU - Wu, C. S.

AU - Barrett, J.

AU - Dang, C. V.

PY - 1996

Y1 - 1996

N2 - The c-Myc oncoprotein is a transcription factor known to participate in cell proliferation, apoptosis, and cell transformation. It is widely believed that c-Myc promotes oncogenesis by transactivating genes that regulate cell growth. Recently cMyc mediated repression of promoters containing an initiator element (Inr) has also been reported but its relevance to cell transformation remains unknown. The Inr is a pyrimidine-rich DNA sequence found in several TATA-less promoters of genes that are regulated during differentiation. We chose to delineate c-Myc transcriptional repression through the Inr in transient transfection assays using the adenoviral major late {adML) promoter which contains two Myc binding sites and an Inr. Methods/Results: We observed that c-Myc represses the adML promoter through the initiator element. To determine which functional domains of the c-Myc protein are necessary for transcriptional repression, we used Myc deletion mutants in similar experiments and found that amino acids 106-143 of the c-Myc transactivation domain and the dimerization motif are required for transcriptional repression. We then examined the transcription and transformation properties of a lymphoma-derived mutant, MycB2, that contains a mutation (115-Phe) within one region critical for repression. This mutant repressed transcription to a greater extent than wild-type cMyc. The mutant also conferred a greater cell growth potential than wild-type c-Myc in soft-anchorage independent growth and ras cotransformation assays. Conclusion: These findings link c-Myc transcriptional repression with cell transformation, thus posing an additional mechanism by which c-Myc could potentially transform cells.

AB - The c-Myc oncoprotein is a transcription factor known to participate in cell proliferation, apoptosis, and cell transformation. It is widely believed that c-Myc promotes oncogenesis by transactivating genes that regulate cell growth. Recently cMyc mediated repression of promoters containing an initiator element (Inr) has also been reported but its relevance to cell transformation remains unknown. The Inr is a pyrimidine-rich DNA sequence found in several TATA-less promoters of genes that are regulated during differentiation. We chose to delineate c-Myc transcriptional repression through the Inr in transient transfection assays using the adenoviral major late {adML) promoter which contains two Myc binding sites and an Inr. Methods/Results: We observed that c-Myc represses the adML promoter through the initiator element. To determine which functional domains of the c-Myc protein are necessary for transcriptional repression, we used Myc deletion mutants in similar experiments and found that amino acids 106-143 of the c-Myc transactivation domain and the dimerization motif are required for transcriptional repression. We then examined the transcription and transformation properties of a lymphoma-derived mutant, MycB2, that contains a mutation (115-Phe) within one region critical for repression. This mutant repressed transcription to a greater extent than wild-type cMyc. The mutant also conferred a greater cell growth potential than wild-type c-Myc in soft-anchorage independent growth and ras cotransformation assays. Conclusion: These findings link c-Myc transcriptional repression with cell transformation, thus posing an additional mechanism by which c-Myc could potentially transform cells.

UR - http://www.scopus.com/inward/record.url?scp=33749440454&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749440454&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33749440454

VL - 44

JO - Journal of Investigative Medicine

JF - Journal of Investigative Medicine

SN - 1081-5589

IS - 3

ER -