Abstract
Histone deacetylases (HDACs) are evolutionary conserved enzymes which operate by removing acetyl groups from histones and other protein regulatory factors, with functional consequences on chromatin remodeling and gene expression profiles. We provide here a review on the recent knowledge accrued on the zinc-dependent HDAC protein family across different species, tissues, and human pathologies, specifically focusing on the role of HDAC inhibitors as anti-cancer agents. We will investigate the chemical specificity of different HDACs and discuss their role in the human interactome as members of chromatin-binding and regulatory complexes.
Highlights
Histone deacetylases (HDACs) constitute a family of proteins highly conserved across all eukaryotes [1]
HDAC-encoding genes are present in all eukaryotes and likely originated from ancestral acetyl-binding enzymes, which are present across all kingdoms of life [10]: the conservation of their aminoacidic sequence and overall function has allowed scientists to transfer the molecular knowledge between model organisms during the past decades
It has been demonstrated that the catalytic activity of endogenous HDAC3 requires the interaction with deacetylase-activating domain (DAD) domain of either the NCOR1 or SMRT [170] and, according to their biological function as a complex, NCOR1, SMRT, and HDAC3 have been observed to be upregulated in numerous types of cancer including colon, lung, prostate, and breast cancers
Summary
Histone deacetylases (HDACs) constitute a family of proteins highly conserved across all eukaryotes [1]. Their main action consists in removing acetyl groups from DNA-binding histone proteins, which is generally associated to a decrease in chromatin accessibility for transcription factors (TFs) and specific, repressive effects on gene expression [2]. Understanding the complexity of HDAC function in cells is of paramount importance to design pharmacological strategies to inhibit or modulate their action in the insurgence and sustenance of pathogenesis. We will show the role of HDACs in human pathogenesis, focusing on cancer, concurrently providing an overview on the current drugs adopted in the inhibition and modulation of HDAC activity
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