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  • Original Paper
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Dynamic in vivo interactions among Myc network members

Oncogene volume 20, pages 4650–4664 (2001)Cite this article

An Editorial Expression of Concern to this article was published on 29 July 2021

16 February 2021 Editor’s Note: an editor's note previously added to this article has been removed because the question raised proved to be without basis.

This article has been updated

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.

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Change history

  • 16 February 2021

    Editor’s Note: an editor's note previously added to this article has been removed because the question raised proved to be without basis.

  • 29 July 2021

    An Editorial Expression of Concern to this paper has been published: https://doi.org/10.1038/s41388-021-01953-9

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Acknowledgements

We thank Ciprian Almonte and Sean Albert for confocal microscopy, to Dorothea Becker for comments on the manuscript, and to Ron Berezney and Suri Somanathan for helpful advice and discussions. This work was supported by NIH grants HL33741 and CA 78259 to EV Prochownik and by an NCI Cancer Center Core Grant to The University of Pittsburgh Cancer Institute.

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Authors and Affiliations

  1. Department of Pediatrics, Section of Hematology/Oncology, Children's Hospital of Pittsburgh, Pittsburgh, 15213, Pennsylvania, PA, USA

    Xiao-ying Yin, Melanie F Landay & Edward V Prochownik

  2. Department of Pharmacology, The University of Pittsburgh Medical Center, Pittsburgh, 15213, Pennsylvania, PA, USA

    Weiping Han & Edwin S Levitan

  3. Department of Cell Biology and Physiology, The University of Pittsburgh Medical Center, Pittsburgh, 15213, Pennsylvania, PA, USA

    Simon C Watkins

  4. Department of Molecular Genetics and Biochemistry, The University of Pittsburgh Medical Center, Pittsburgh, 15213, Pennsylvania, PA, USA

    Edward V Prochownik

  5. The University of Pittsburgh Cancer Institute, Pittsburgh, 15213, Pennsylvania, PA, USA

    Simon C Watkins & Edward V Prochownik

  6. Center for Light Microscope Imaging and Biotechnology, Carnegie-Mellon University, Pittsburgh, 15213, Pennsylvania, PA, USA

    Richard M Levenson & Daniel L Farkas

  7. Department of Bioengineering, The University of Pittsburgh, Pittsburgh, 15213, Pennsylvania, PA, USA

    Daniel L Farkas

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  1. Xiao-ying Yin
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Correspondence to Edward V Prochownik.

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Yin, Xy., Landay, M., Han, W. et al. Dynamic in vivo interactions among Myc network members. Oncogene 20, 4650–4664 (2001). https://doi.org/10.1038/sj.onc.1204606

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