title: Molecular pathways: old drugs define new pathways: non-histone acetylation at the crossroads of the DNA damage response and autophagy.
abstract: Histone deacetylases (HDAC) modulate acetylation and the function of histone and non-histone proteins. HDAC inhibitors have been developed to block the aberrant action of HDACs in cancer, and several are in clinical use (vorinostat, romidepsin, and valproic acid). Detailed understanding of their action is lacking, however, and their clinical activity is limited in most cases. Recently, HDACs have been involved in the control of the DNA damage response (DDR) at several levels and in directly regulating the acetylation of a number of DDR proteins (including CtIP and Exo1). Mechanistically, acetylation leads to the degradation of double-strand break repair enzymes through autophagy, providing a novel, direct link between DDR and autophagy. These observations, obtained in yeast cells, should now be translated to mammalian model systems and cancer cells to reveal whether this acetylation link is maintained in mammals, and if and how it is deregulated in cancer. In addition to HDACs, DDR and autophagy have been addressed pharmacologically, suggesting that the acetylation link, if involved in cancer, can be exploited for the design of new anticancer treatments.
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Oronza Antonietta
authors.initials: OA
authors.lastname: Botrugno
authors.forename: Thomas
authors.initials: T
authors.lastname: Robert
authors.forename: Fabio
authors.initials: F
authors.lastname: Vanoli
authors.forename: Marco
authors.initials: M
authors.lastname: Foiani
authors.forename: Saverio
authors.initials: S
authors.lastname: Minucci
mesh_terms: D000107:Acetylation; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001343:Autophagy; D002986:Clinical Trials as Topic; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006655:Histone Deacetylases