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BRD4 and MYC: power couple in transcription and disease

Journal

FEBS JOURNAL
Volume 290, Issue 20, Pages 4820-4842

Publisher

WILEY
DOI: 10.1111/febs.16580

Keywords

BRD4 histone acetyltransferase; BRD4 kinase; chromatin remodelling; MYC; transcription

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The MYC proto-oncogene and BRD4 protein play essential roles in cell biology and disease, with their functions and regulation closely interlinked. They regulate gene expression, maintain chromatin structure, and ensure genome stability, and dysregulation can lead to diseases, particularly cancer.
The MYC proto-oncogene and BRD4, a BET family protein, are two cardinal proteins that have a broad influence in cell biology and disease. Both proteins are expressed ubiquitously in mammalian cells and play central roles in controlling growth, development, stress responses and metabolic function. As chromatin and transcriptional regulators, they play a critical role in regulating the expression of a burgeoning array of genes, maintaining chromatin architecture and genome stability. Consequently, impairment of their function or regulation leads to many diseases, with cancer being the most predominant. Interestingly, accumulating evidence indicates that regulation of the expression and functions of MYC are tightly intertwined with BRD4 at both transcriptional and post-transcriptional levels. Here, we review the mechanisms by which MYC and BRD4 are regulated, their functions in governing various molecular mechanisms and the consequences of their dysregulation that lead to disease. We present a perspective of how the regulatory mechanisms for the two proteins could be entwined at multiple points in a BRD4-MYC nexus that leads to the modulation of their functions and disease upon dysregulation.

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