The Emerging Role of Histone Deacetylases (HDACs) in UPR Regulation

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.