ARDent about acetylation and deacetylation in hypoxia signalling.
Given the key role that the alpha subunit of the alphabeta heterodimeric transcription factor hypoxia-inducible factor-1 (HIF-1) has in tumourigenesis, and in particular in angiogenesis, a full understanding of its regulation is crucial to the development of cancer therapeutics. Posttranslational acetylation and deacetylation of this subunit by an acetyltransferase called Arrest-defective-1 (ARD1) and by different histone deacetylases (HDACs), respectively, has been suggested as a mechanism. However, conflicting data bring into question the foundations of this mechanism and at present it is not clear what the precise role of these proteins is with respect to HIF. Nonetheless, the observation that small-molecule inhibitors of HDACs have anti-angiogenic activity suggests that acetylation and deacetylation of HIF or HIF modifiers represents a potential target in cancer therapy.
Bilton
Rebecca
R
Institute of Signaling, Developmental Biology and Cancer Research CNRS UMR 6543, University of Nice, Centre A. Lacassagne, 33 Avenue Valombrose, 06189 Nice, France.
Trottier
Eric
E
Pouysségur
Jacques
J
Brahimi-Horn
M Christiane
MC
D000107:Acetylation / Q000187:drug effects; D000123:Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D015195:Drug Design; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D063209:N-Terminal Acetyltransferase A; D063213:N-Terminal Acetyltransferase E; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D056572:Histone Deacetylase Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020033:Protein Isoforms; D000123:Acetyltransferases; D063209:N-Terminal Acetyltransferase A; C504824:NAA10 protein, human; D063213:N-Terminal Acetyltransferase E; D006655:Histone Deacetylases