Cited by 311Genomics and Chromatin DynamicsCancer-related Molecular PathwaysChromatin Remodeling and Cancer

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Target gene-independent functions of MYC oncoproteins

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Baluapuri, Apoorva, Wolf, Elmar, Eilers, Martin·2020·Nature Reviews Molecular Cell Biology

DOI 10.1038/s41580-020-0215-2PMC PMC7611238

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Abstract

Oncoproteins of the MYC family are major drivers of human tumorigenesis. Since a large body of evidence indicates that MYC proteins are transcription factors, studying their function has focused on the biology of their target genes. Detailed studies of MYC-dependent changes in RNA levels have provided contrasting models of the oncogenic activity of MYC proteins through either enhancing or repressing the expression of specific target genes, or as global amplifiers of transcription. In this Review, we first summarize the biochemistry of MYC proteins and what is known (or is unclear) about the MYC target genes. We then discuss recent progress in defining the interactomes of MYC and MYCN and how this information affects central concepts of MYC biology, focusing on mechanisms by which MYC proteins modulate transcription. MYC proteins promote transcription termination upon stalling of RNA polymerase II, and we propose that this mechanism enhances the stress resilience of basal transcription. Furthermore, MYC proteins coordinate transcription elongation with DNA replication and cell cycle progression. Finally, we argue that the mechanism by which MYC proteins regulate the transcription machinery is likely to promote tumorigenesis independently of global or relative changes in the expression of their target genes.

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Authors: Baluapuri, A., Wolf, E., & Eilers, M.
Affiliations: University of Würzburg (DE)
Corresponding author: Eilers, Martin
ORCID: Baluapuri, Apoorva
Wolf, Elmar
Eilers, Martin
Venue: Nature Reviews Molecular Cell Biology
Publisher: Springer Science and Business Media LLC
Published: 2020-02-18
Volume: 21
Issue: 5
Pages: 255-267
ISSN: 1471-0072 (ISSN-L)
1471-0080
DOI: 10.1038/s41580-020-0215-2
PMC: PMC7611238
OpenAlex: W3007097494
Cited by: 310
References: 130
Citations by year: 2026: 29 · 2025: 48 · 2024: 63 · 2023: 60 · 2022: 50 · 2021: 51 · 2020: 9
FWCI: 4.09
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Reviews Molecular Cell Biology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: Myc oncoprotein, MYCN, transcription factors, target genes, RNA polymerase II stalling, transcription termination, transcription elongation, DNA replication, cell cycle progression, stress resilience, basal transcription, carcinogenesis, protein-protein interaction network, transcriptional regulation
MeSH terms: N-Myc Proto-Oncogene Protein, Cell Cycle, DNA Replication, Humans, Neoplasms, Transcription Factors, Transcription, Genetic, Oncogene Proteins, Proto-Oncogene Proteins c-myc, Cell Proliferation, Carcinogenesis

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