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MYC cofactors: molecular switches controlling diverse biological outcomes
1Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2175.
Abstract:
The transcription factor MYC has fundamental roles in proliferation, apoptosis, tumorigenesis, and stem cell pluripotency. Over the last 30 years extensive information has been gathered on the numerous cofactors that interact with MYC and the target genes that are regulated by MYC as a means of understanding the molecular mechanisms controlling its diverse roles. Despite significant advances and perhaps because the amount of information learned about MYC is overwhelming, there has been little consensus on the molecular functions of MYC that mediate its critical biological roles. In this perspective, the major MYC cofactors that regulate the various transcriptional activities of MYC, including canonical and noncanonical transactivation and transcriptional repression, will be reviewed and a model of how these transcriptional mechanisms control MYC-mediated proliferation, apoptosis, and tumorigenesis will be presented. The basis of the model is that a variety of cofactors form dynamic MYC transcriptional complexes that can switch the molecular and biological functions of MYC to yield a diverse range of outcomes in a cell-type- and context-dependent fashion.
Insights
MYC protein interactions with cofactors dynamically regulate gene expression. This dynamic regulation controls cell proliferation, apoptosis, and tumorigenesis based on cell type and context.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The transcription factor MYC is crucial for cell proliferation, apoptosis, and tumorigenesis.
- Decades of research have identified numerous MYC cofactors and target genes, yet consensus on MYC's molecular functions remains elusive.
- Understanding MYC's complex roles requires a deeper look into its cofactor interactions.
Purpose of the Study:
- To review major MYC cofactors and their roles in MYC's transcriptional activities.
- To present a model explaining how MYC-cofactor complexes control MYC-mediated biological processes.
- To elucidate the context-dependent nature of MYC functions.
Main Methods:
- Literature review of MYC cofactors and their interactions.
- Analysis of canonical and noncanonical transactivation and transcriptional repression mechanisms.
- Development of a model for dynamic MYC transcriptional complex formation.
Main Results:
- MYC cofactors significantly influence MYC's transcriptional activities, including activation and repression.
- Dynamic MYC-cofactor complexes are central to MYC's diverse functions.
- These complexes enable context- and cell-type-specific outcomes.
Conclusions:
- MYC's diverse biological roles are mediated by dynamic transcriptional complexes.
- Cofactor interactions allow MYC to switch molecular and biological functions.
- This dynamic model provides a framework for understanding MYC in proliferation, apoptosis, and cancer.
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