Dynamic in vivo interactions among Myc network members

Xiao Ying Yin, Melanie F. Landay, Weiping Han, Edwin S. Levitan, Simon C. Watkins, Richard M Levenson, Daniel L. Farkas, Edward V. Prochownik

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Members of the Myc oncoprotein network (c-Myc, Max, and Mad) play important roles in proliferation, differentiation, and apoptosis. We expressed chimeric green fluorescent protein (GFP) fusions of c-Myc, Max, and three Mad proteins in fibroblasts. Individually, c-Myc and Mad proteins localized in subnuclear speckles, whereas Max assumed a homogeneous nuclear pattern. These distributions were co-dominant and dynamic, however, as each protein assumed the pattern of its heterodimeric partner when the latter was co-expressed at a higher level. Deletion mapping of two Mad members, Mad1 and Mxi1, demonstrated that the domains responsible for nuclear localization and speckling are separable. A non-speckling Mxi1 mutant was also less effective as a transcriptional repressor than wild-type Mxi1. c-Myc nuclear speckles were distinct from SC-35 domains involved in mRNA processing. However, in the presence of co-expressed Max, c-Myc, but not Mad, co-localized to a subset of SC-35 loci. These results show that Myc network proteins comprise dynamic subnuclear structures and behave co-dominantly when co-expressed with their normal heterodimerization partners. In addition, c-Myc-Max heterodimers, but not Max-Mad heterodimers, localize to foci actively engaged in pre-mRNA transcription/processing. These findings suggest novel means by which Myc network members promote transcriptional activation or repression.

Original languageEnglish (US)
Pages (from-to)4650-4664
Number of pages15
JournalOncogene
Volume20
Issue number34
DOIs
StatePublished - Aug 2 2001
Externally publishedYes

Keywords

  • Green fluorescent protein (GFP)
  • Mad Mxi1
  • Max
  • SC-35
  • Transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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  • Cite this

    Yin, X. Y., Landay, M. F., Han, W., Levitan, E. S., Watkins, S. C., Levenson, R. M., Farkas, D. L., & Prochownik, E. V. (2001). Dynamic in vivo interactions among Myc network members. Oncogene, 20(34), 4650-4664. https://doi.org/10.1038/sj.onc.1204606