The multifaceted role of lysine acetylation in cancer: prognostic biomarker and therapeutic target.
Lysine acetylation is a post-translational modification that regulates gene transcription by targeting histones as well as a variety of transcription factors in the nucleus. Recently, several reports have demonstrated that numerous cytosolic proteins are also acetylated and that this modification, affecting protein activity, localization and stability has profound consequences on their cellular functions. Interestingly, most non-histone proteins targeted by acetylation are relevant for tumorigenesis. In this review, we will analyze the functional implications of lysine acetylation in different cellular compartments, and will examine our current understanding of lysine acetyltransferases family, highlighting the biological role and prognostic value of these enzymes and their substrates in cancer. The latter part of the article will address challenges and current status of molecules targeting lysine acetyltransferase enzymes in cancer therapy.
Preclinical Models and New Therapeutic Agents Unit, Research, Advanced Diagnostics and Technological Innovation Department, Regina Elena National Cancer Institute, Rome, Italy.
Marta
M
Di Martile
Preclinical Models and New Therapeutic Agents Unit, Research, Advanced Diagnostics and Technological Innovation Department, Regina Elena National Cancer Institute, Rome, Italy.
Donatella
D
Del Bufalo
Preclinical Models and New Therapeutic Agents Unit, Research, Advanced Diagnostics and Technological Innovation Department, Regina Elena National Cancer Institute, Rome, Italy.
Daniela
D
Trisciuoglio
D000107:Acetylation; D000123:Acetyltransferases / Q000502:physiology; D000818:Animals; D015415:Biomarkers; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D000070837:Lysine Acetyltransferases / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008868:Microtubule Proteins; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011379:Prognosis; D011499:Protein Processing, Post-Translational; D050880:p300-CBP Transcription Factors / Q000502:physiology; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D015415:Biomarkers; D008239:Lysine; D000070837:Lysine Acetyltransferases; D008868:Microtubule Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C583619:ATAT1 protein, mouse
KAT inhibitors; cancer; lysine acetylation; lysine acetyltransferases