An essential domain of the c-Myc protein interacts with a nuclear factor that is also required for E1A-mediated transformation

D. E. Brough, T. J. Hofmann, K. B. Ellwood, R. A. Townley, M. D. Cole

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Cell transformation by nuclear oncogenes such as c-myc presumably involves the transcriptional activation of a set of target genes that participate in the control of cell division. The function of a small evolutionarily conserved domain of the c-myc gene encompassing amino acids 129 to 145 was analyzed to explore the relationship between cell transformation and transcriptional activation. Deletion of this domain inactivated the c-myc oncogene for cell transformation while retaining the ability to activate transcription of either myc consensus binding sites or a GAL4-dependent promoter when the c-myc N-terminus was fused to the GAL4 DNA-binding domain. Point mutations that altered a conserved tryptophan (amino acid 136) within this domain had similar effects. Expression of the wt c-Myc N terminus (amino acids 1 to 262) as a GAL4 fusion was a dominant inhibitor of cell transformation by the c-myc oncogene, and this same domain also inhibited transformation by the adenovirus E1A gene. Surprisingly, deletion of amino acids 129 to 145 eliminated the dominant negative activity of GAL4-Myc on both c-myc and E1A transformation. Expression of the GALA-Myc protein in Cos cells led to the formation of a specific complex between the Myc N terminus and a nuclear factor, and this complex was absent with the dl129-145 mutant. These results suggest that an essential domain of the c-Myc protein interacts with a specific nuclear factor that is also required for E1A transformation.

Original languageEnglish (US)
Pages (from-to)1536-1544
Number of pages9
JournalMolecular and Cellular Biology
Volume15
Issue number3
StatePublished - 1995
Externally publishedYes

Fingerprint

Proto-Oncogene Proteins c-myc
myc Genes
Amino Acids
Transcriptional Activation
Oncogenes
Point Mutation
Adenoviridae
Tryptophan
Cell Division
Genes
Binding Sites
DNA
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

Brough, D. E., Hofmann, T. J., Ellwood, K. B., Townley, R. A., & Cole, M. D. (1995). An essential domain of the c-Myc protein interacts with a nuclear factor that is also required for E1A-mediated transformation. Molecular and Cellular Biology, 15(3), 1536-1544.

An essential domain of the c-Myc protein interacts with a nuclear factor that is also required for E1A-mediated transformation. / Brough, D. E.; Hofmann, T. J.; Ellwood, K. B.; Townley, R. A.; Cole, M. D.

In: Molecular and Cellular Biology, Vol. 15, No. 3, 1995, p. 1536-1544.

Research output: Contribution to journalArticle

Brough, D. E. ; Hofmann, T. J. ; Ellwood, K. B. ; Townley, R. A. ; Cole, M. D. / An essential domain of the c-Myc protein interacts with a nuclear factor that is also required for E1A-mediated transformation. In: Molecular and Cellular Biology. 1995 ; Vol. 15, No. 3. pp. 1536-1544.
@article{a5310eb3eeef4b34a9cc630f295be30c,
title = "An essential domain of the c-Myc protein interacts with a nuclear factor that is also required for E1A-mediated transformation",
abstract = "Cell transformation by nuclear oncogenes such as c-myc presumably involves the transcriptional activation of a set of target genes that participate in the control of cell division. The function of a small evolutionarily conserved domain of the c-myc gene encompassing amino acids 129 to 145 was analyzed to explore the relationship between cell transformation and transcriptional activation. Deletion of this domain inactivated the c-myc oncogene for cell transformation while retaining the ability to activate transcription of either myc consensus binding sites or a GAL4-dependent promoter when the c-myc N-terminus was fused to the GAL4 DNA-binding domain. Point mutations that altered a conserved tryptophan (amino acid 136) within this domain had similar effects. Expression of the wt c-Myc N terminus (amino acids 1 to 262) as a GAL4 fusion was a dominant inhibitor of cell transformation by the c-myc oncogene, and this same domain also inhibited transformation by the adenovirus E1A gene. Surprisingly, deletion of amino acids 129 to 145 eliminated the dominant negative activity of GAL4-Myc on both c-myc and E1A transformation. Expression of the GALA-Myc protein in Cos cells led to the formation of a specific complex between the Myc N terminus and a nuclear factor, and this complex was absent with the dl129-145 mutant. These results suggest that an essential domain of the c-Myc protein interacts with a specific nuclear factor that is also required for E1A transformation.",
author = "Brough, {D. E.} and Hofmann, {T. J.} and Ellwood, {K. B.} and Townley, {R. A.} and Cole, {M. D.}",
year = "1995",
language = "English (US)",
volume = "15",
pages = "1536--1544",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "3",

}

TY - JOUR

T1 - An essential domain of the c-Myc protein interacts with a nuclear factor that is also required for E1A-mediated transformation

AU - Brough, D. E.

AU - Hofmann, T. J.

AU - Ellwood, K. B.

AU - Townley, R. A.

AU - Cole, M. D.

PY - 1995

Y1 - 1995

N2 - Cell transformation by nuclear oncogenes such as c-myc presumably involves the transcriptional activation of a set of target genes that participate in the control of cell division. The function of a small evolutionarily conserved domain of the c-myc gene encompassing amino acids 129 to 145 was analyzed to explore the relationship between cell transformation and transcriptional activation. Deletion of this domain inactivated the c-myc oncogene for cell transformation while retaining the ability to activate transcription of either myc consensus binding sites or a GAL4-dependent promoter when the c-myc N-terminus was fused to the GAL4 DNA-binding domain. Point mutations that altered a conserved tryptophan (amino acid 136) within this domain had similar effects. Expression of the wt c-Myc N terminus (amino acids 1 to 262) as a GAL4 fusion was a dominant inhibitor of cell transformation by the c-myc oncogene, and this same domain also inhibited transformation by the adenovirus E1A gene. Surprisingly, deletion of amino acids 129 to 145 eliminated the dominant negative activity of GAL4-Myc on both c-myc and E1A transformation. Expression of the GALA-Myc protein in Cos cells led to the formation of a specific complex between the Myc N terminus and a nuclear factor, and this complex was absent with the dl129-145 mutant. These results suggest that an essential domain of the c-Myc protein interacts with a specific nuclear factor that is also required for E1A transformation.

AB - Cell transformation by nuclear oncogenes such as c-myc presumably involves the transcriptional activation of a set of target genes that participate in the control of cell division. The function of a small evolutionarily conserved domain of the c-myc gene encompassing amino acids 129 to 145 was analyzed to explore the relationship between cell transformation and transcriptional activation. Deletion of this domain inactivated the c-myc oncogene for cell transformation while retaining the ability to activate transcription of either myc consensus binding sites or a GAL4-dependent promoter when the c-myc N-terminus was fused to the GAL4 DNA-binding domain. Point mutations that altered a conserved tryptophan (amino acid 136) within this domain had similar effects. Expression of the wt c-Myc N terminus (amino acids 1 to 262) as a GAL4 fusion was a dominant inhibitor of cell transformation by the c-myc oncogene, and this same domain also inhibited transformation by the adenovirus E1A gene. Surprisingly, deletion of amino acids 129 to 145 eliminated the dominant negative activity of GAL4-Myc on both c-myc and E1A transformation. Expression of the GALA-Myc protein in Cos cells led to the formation of a specific complex between the Myc N terminus and a nuclear factor, and this complex was absent with the dl129-145 mutant. These results suggest that an essential domain of the c-Myc protein interacts with a specific nuclear factor that is also required for E1A transformation.

UR - http://www.scopus.com/inward/record.url?scp=0028883262&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028883262&partnerID=8YFLogxK

M3 - Article

C2 - 7862146

AN - SCOPUS:0028883262

VL - 15

SP - 1536

EP - 1544

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 3

ER -