Nonhistone targets of KAT2A and KAT2B implicated in cancer biology

Abstract

Lysine acetylation is a critical post-translation modification that can impact a protein's localization, stability, and function. Originally thought to only occur on histones, we now know thousands of nonhistone proteins are also acetylated. In conjunction with many other proteins, lysine acetyltransferases (KATs) are incorporated into large protein complexes that carry out these modifications. In this review we focus on the contribution of two KATs, KAT2A and KAT2B, and their potential roles in the development and progression of cancer. Systems biology demands that we take a broad look at protein function rather than focusing on individual pathways or targets. As such, in this review we examine KAT2A/2B-directed nonhistone protein acetylations in cancer in the context of the 10 "Hallmarks of Cancer", as defined by Hanahan and Weinberg. By focusing on specific examples of KAT2A/2B-directed acetylations with well-defined mechanisms or strong links to a cancer phenotype, we aim to reinforce the complex role that these enzymes play in cancer biology.

Kat2a and Kat2b Acetyltransferase Activity Regulates Craniofacial Cartilage and Bone Differentiation in Zebrafish and Mice

“…Another substrate of Kat2b, Akt1, has been found to be correlated to the regulation of neural crest cells specification and migration [91] and embryonic skeletal development [92], and mutated in patients with craniofacial defects, including mandible and frontal bone deformities [93]. In addition, acetylation of Akt1 by Kat2b has been shown to regulate cell proliferation and survival in vitro [61,94,95]. Thus, it is clear that Kat2b regulates other factors directly, and not via the modification of H3K9.…”

“…Kat2a and Kat2b regulate various physiological phenomenon, including embryonic development, brown adipogenesis, transcription, genome stability, cancer, immune response, and angiogenesis [56,57,58,59,60,61]. In this study, we specifically focused on their role in early developmental stages of the craniofacial skeleton, which is not well-understood.…”

Integrated Analysis of the Functions and Prognostic Values of RNA-Binding Proteins in Colorectal Cancer

“…Non-sense-mediated mRNA decay (NMD) is one of the most common mRNA surveillance, which is involved in the detection and decay of mRNAs containing premature termination codons (Hentze and Kulozik, 1999). Inhibition of the oncogenic activity of NMD, producing several encoded mutant proteins with deleterious activity, may be an effective strategy for the personalized treatment of microsatellite instability CRC (Bokhari et al, 2018). Tumor suppressor genes are prone to NMD-induced nonsense mutations, which were reported in a series of tumors, including stomach cancer, ovarian cancer, ovarian cancer, breast cancer, and kidney cancer (Popp and Maquat, 2018).…”

“…Moreover, KAT2B acetylates non-histone proteins (Choudhary et al, 2009;Downey and Baetz, 2016), which has been reported to be a critical regulator of p53-dependent p21 expression in response to multiple p53-activating stresses (Love et al, 2012). KAT2B also plays a role in the development and progression of cancer (Bondy-Chorney et al, 2019). Thus, KAT2B may be involved in CRC progression through regulating TDRD6, ZC3H12C, and RBM47.…”

Integrative Data Analytic Framework to Enhance Cancer Precision Medicine

“…In addition, KAT2B (PCAF) activity has been linked to cancers, and in particular, to breast cancers, in the literature. [37][38][39] MDM2 has also been associated with breast cancer. 40 SP1 expression has been linked to breast cancer in multiple prior studies.…”