Oncogenic activity of the c-Myc protein requires dimerization with Max

Bruno Amati, Mary W. Brooks, Naomi Levy, Trevor D. Littlewood, Gerard I. Evan, Hartmut Land

Research output: Contribution to journalArticle

391 Citations (Scopus)

Abstract

c-Myc (Myc) and Max proteins dimerize and bind DNA through basic-helix-loop-helix-leucine zipper motifs (b-HLH-LZ). Using a genetic approach, we demonstrate that binding to Max is essential for Myc transforming activity and that Myc homodimers are inactive. Mutants of Myc and Max that bind efficiently to each other but not to their wild-type partners were generated by either exchanging the HLH-LZ domains or reciprocally modifying LZ dimerization specificities. While transformation defective on their own, complementary mutants restore Myc transforming activity when coexpressed in cells. The HLH-LZ exchange mutants also have dominant negative activity on wild-type Myc function. In addition, wild-type max antagonizes myc function in a dose-dependent manner, presumably through competition of Max-Max and Myc-Max dimers for common target DNA sites. Therefore, Max can function as both suppressor and activator of Myc. A general model for the role of Myc and Max in growth control is discussed.

Original languageEnglish
Pages (from-to)233-245
Number of pages13
JournalCell
Volume72
Issue number2
DOIs
Publication statusPublished - Jan 29 1993

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Protein Multimerization
Proto-Oncogene Proteins c-myc
Dimerization
Leucine Zippers
DNA
Dimers
Growth

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Amati, B., Brooks, M. W., Levy, N., Littlewood, T. D., Evan, G. I., & Land, H. (1993). Oncogenic activity of the c-Myc protein requires dimerization with Max. Cell, 72(2), 233-245. https://doi.org/10.1016/0092-8674(93)90663-B

Oncogenic activity of the c-Myc protein requires dimerization with Max. / Amati, Bruno; Brooks, Mary W.; Levy, Naomi; Littlewood, Trevor D.; Evan, Gerard I.; Land, Hartmut.

In: Cell, Vol. 72, No. 2, 29.01.1993, p. 233-245.

Research output: Contribution to journalArticle

Amati, B, Brooks, MW, Levy, N, Littlewood, TD, Evan, GI & Land, H 1993, 'Oncogenic activity of the c-Myc protein requires dimerization with Max', Cell, vol. 72, no. 2, pp. 233-245. https://doi.org/10.1016/0092-8674(93)90663-B
Amati B, Brooks MW, Levy N, Littlewood TD, Evan GI, Land H. Oncogenic activity of the c-Myc protein requires dimerization with Max. Cell. 1993 Jan 29;72(2):233-245. https://doi.org/10.1016/0092-8674(93)90663-B
Amati, Bruno ; Brooks, Mary W. ; Levy, Naomi ; Littlewood, Trevor D. ; Evan, Gerard I. ; Land, Hartmut. / Oncogenic activity of the c-Myc protein requires dimerization with Max. In: Cell. 1993 ; Vol. 72, No. 2. pp. 233-245.
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