The emerging role of histone deacetylases (HDACs) in UPR regulation

Department of Experimental Therapeutics and Radiation Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Methods in enzymology (Impact Factor: 2.09). 01/2011; 490:159-74. DOI: 10.1016/B978-0-12-385114-7.00010-6
Source: PubMed


Although the function of histone deacetylases (HDACs) have primarily been associated with influencing transcription through chromatin remodeling, the capacity of these enzymes to interface with a diverse array of biologic processes by modulating a growing list of nonhistone substrates has gained recent attention. Recent investigations have demonstrated the potential of HDACs to directly regulate the unfolded protein response (UPR) through acetylation of its central regulatory protein, Grp78. Further, this appears to be an important mechanism underlying the anti-tumor activity of HDAC inhibitors. Herein, we provide a summary of the literature supporting the role HDACs play in regulating the UPR and a detailed description of methods to allow for the study of both acetylation of nonhistone proteins and UPR pathway activation following HDAC inhibition.

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    • "Histone deacetylase inhibitors induce apoptosis by dowregulation of Bcl-2 family members (Mitsiades et al, 2003; Khan et al, 2004) and overcome drug resistance mediated by the BM environment (Mitsiades et al, 2003). Furthermore, glucose-regulated protein 78 (GRP78) was recently identified as a novel non-histone target of HDACi (Rao et al, 2010; Kahali et al, 2011). Glucose-regulated protein 78 has a central role in the unfolded protein response (UPR). "
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