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Review
. 2016 Aug 23;7(34):55789-55810.
doi: 10.18632/oncotarget.10048.

The multifaceted role of lysine acetylation in cancer: prognostic biomarker and therapeutic target

Marta Di Martile  1 , Donatella Del Bufalo  1 , Daniela Trisciuoglio  1
Affiliations
Review

The multifaceted role of lysine acetylation in cancer: prognostic biomarker and therapeutic target

Marta Di Martile et al. Oncotarget. .

Abstract

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.

Keywords: KAT inhibitors; cancer; lysine acetylation; lysine acetyltransferases.

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Conflict of interest statement

CONFLICTS OF INTEREST

No potential conflicts of interest were disclosed.

Figures

Figure 2
Figure 2. Lysine (K) acetylation is a reversible post-translational modification of proteins, including histones, transcription factors as well as metabolic enzymes and other nuclear and cytoplasmic proteins
Proteins can be acetylated at lysine residues (Ac-K) by specific enzymes, called lysine acetyltransferases (KATs), or deacetylated by Zn2+-dependent histone deacetylases (HDACs) and NAD+-dependent sirtuin deacetylases (SIRTs). Acetylation levels are tightly regulated by these enzymes and can impact the biological function of different proteins, some of them are here reported. PTM: post-translational modifications.
Figure 2
Figure 2. Schematic overview of nuclear, cytoplasmic and organelle-specific mechanisms regulated by acetylation
Lysine acetylation is well known to play a key role in regulating gene transcription and other DNA-dependent nuclear processes. Proteomics studies have identified many possible substrates of lysine acetylation and a large fraction of them resides in the cytoplasmic compartment, implicating their involvement in regulating important cellular pathways.
Figure 3
Figure 3. Role of main and well-studied lysine acetyltransferases (KATs) in cancer biology
KATs have an important role in transcription regulation and they participate in the expression of malignant phenotypes in cancer cells.
See this image and copyright information in PMC

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