Epigenetic pathway-BRD4
In normal cells, gene expression is tightly controlled by epigenetic mechanisms that regulate chromatin accessibility for the transcriptional machinery through post-translational modifications of histones (e.g., methylation, acetylation, and phosphorylation) and DNA (methylation and hydroxymethylation). Modified chromatin in turn recruits ‘reader’ proteins to carry out further regulatory functions. However, many cancers display global changes in histone modifications, aberrant methylation patterns, and mutations in or altered expression levels of key chromatin-modifying proteins, and some tumors even harbor mutations in histone variants.
BRD4 is a member of the BET (bromodomain and extra terminal domain) family, containing two bromodomains that recognize acetylated lysine residues and an extended C-terminal domain with little sequence homology to other BET family members. BRD4 overexpression is observed in many cancer cells, and its inhibition is associated with the downregulation of c-Myc, following the apoptosis of the cells.
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