Journal
MOLECULAR CELL
Volume 72, Issue 5, Pages 836-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2018.09.031
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Funding
- Canada Research Chairs Program
- Canadian Institutes of Health Research
- Terry Fox new investigator award
- Canadian Institutes of Health Research new investigator award
- Ontario Region Canadian Breast Cancer Foundation
- Natural Sciences and Engineering Research Council of Canada
- AbbVie
- Bayer Pharma AG
- Boehringer Ingelheim
- Canada Foundation for Innovation
- Eshelman Institute for Innovation
- Genome Canada through the Ontario Genomics Institute [OGI-055]
- Innovative Medicines Initiative (EU/EFPIA) (ULTRA-DD) [115766]
- Janssen
- Merck KGaA (Darmstadt, Germany)
- MSD
- Novartis Pharma AG
- Ontario Ministry of Research, Innovation and Science (MRIS)
- Pfizer
- Sao Paulo Research Foundation-FAPESP
- Takeda
- Wellcome
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Transforming members of the MYC family (MYC, MYCL1, and MYCN) encode transcription factors containing six highly conserved regions, termed MYC homology boxes (MBs). By conducting proteomic profiling of the MB interactomes, we demonstrate that half of the MYC interactors require one or more MBs for binding. Comprehensive phenotypic analyses reveal that two MBs, MBO and MBII, are universally required for transformation. MBII mediates interactions with acetyltransferase-containing complexes, enabling histone acetylation, and is essential for MYC-dependent tumor initiation. By contrast, MBO mediates interactions with transcription elongation factors via direct binding to the general transcription factor TFIIF. MBO is dispensable for tumor initiation but is a major accelerator of tumor growth. Notably, the full transforming activity of MYC can be restored by co-expression of the non-transforming MBO and MBII deletion proteins, indicating that these two regions confer separate molecular functions, both of which are required for oncogenic MYC activity.
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