Histone acetyltransferase KAT2A (GCN5) (KAT2A)

Histone acetyltransferase KAT2A, widely known as GCN5, is a pivotal epigenetic enzyme that functions as a lysine acetyltransferase within the GNAT family [1, 4]. It serves as the catalytic core of major transcriptional coactivator complexes, such as SAGA and ATAC, where it acetylates histone H3 (primarily at K9 and K14) to promote an open chromatin state and facilitate gene transcription [7, 14, 16]. Beyond histones, GCN5 modifies numerous non-histone proteins, including the oncogene MYC and the metabolic regulator PGC-1α, thereby influencing cell cycle progression, metabolism, and DNA repair [4, 8, 10]. In clinical contexts, GCN5 is frequently overexpressed in various malignancies, including acute myeloid leukemia and neuroblastoma, where it drives oncogenic programs and stabilizes key transcription factors [11, 14, 17]. Consequently, GCN5 has emerged as a promising therapeutic target, with small-molecule inhibitors like MB-3 and PROTAC degraders such as GSK983 currently under investigation to disrupt its activity in cancer and inflammatory diseases [9, 13, 14]. However, because GCN5 is essential for embryonic development and normal metabolic homeostasis, therapeutic interventions must carefully balance efficacy with potential systemic toxicity [1, 16].

Other names

GCN5GCN5L2PCAF-bhGCN5Lysine acetyltransferase 2AGeneral control of amino acid synthesis protein 5-like 2STAF97HGCN5

Inhibition of the acetyltransferase catalytic activity or targeted degradation of the KAT2A protein to modulate gene expression and chromatin accessibility [9, 13, 14].