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 Citations (Scopus)

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

Fingerprint

Proto-Oncogene Proteins c-myc
Proteins
Oncogene Proteins
RNA Precursors
Green Fluorescent Proteins
Transcriptional Activation
Fibroblasts
Apoptosis
Messenger RNA

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Yin, X. Y., Landay, M. F., Han, W., Levitan, E. S., Watkins, S. C., Levenson, R. M., ... 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

Dynamic in vivo interactions among Myc network members. / Yin, Xiao Ying; Landay, Melanie F.; Han, Weiping; Levitan, Edwin S.; Watkins, Simon C.; Levenson, Richard M; Farkas, Daniel L.; Prochownik, Edward V.

In: Oncogene, Vol. 20, No. 34, 02.08.2001, p. 4650-4664.

Research output: Contribution to journalArticle

Yin, XY, Landay, MF, Han, W, Levitan, ES, Watkins, SC, Levenson, RM, Farkas, DL & Prochownik, EV 2001, 'Dynamic in vivo interactions among Myc network members', Oncogene, vol. 20, no. 34, pp. 4650-4664. https://doi.org/10.1038/sj.onc.1204606
Yin XY, Landay MF, Han W, Levitan ES, Watkins SC, Levenson RM et al. Dynamic in vivo interactions among Myc network members. Oncogene. 2001 Aug 2;20(34):4650-4664. https://doi.org/10.1038/sj.onc.1204606
Yin, Xiao Ying ; Landay, Melanie F. ; Han, Weiping ; Levitan, Edwin S. ; Watkins, Simon C. ; Levenson, Richard M ; Farkas, Daniel L. ; Prochownik, Edward V. / Dynamic in vivo interactions among Myc network members. In: Oncogene. 2001 ; Vol. 20, No. 34. pp. 4650-4664.
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