GCN5/PCAF

GCN5 (KAT2A) and PCAF (KAT2B) are closely related GNAT-family lysine acetyltransferases that acetylate histone and non-histone proteins, thereby regulating chromatin organization, transcription, metabolism, and other fundamental cellular processes^[1]. As catalytic subunits of major chromatin-associated complexes, including SAGA and ATAC, GCN5/PCAF function as transcriptional coactivators and contribute to global histone acetylation as well as locus-specific gene regulation^[2][3][4]. Mechanistically, these enzymes transfer acetyl groups from acetyl-CoA to lysine residues and thereby influence gene expression programs linked to development, cell fate determination, genome integrity, and cellular homeostasis^[1][3][6]. Studies in developmental and disease models further demonstrate that dysregulation of GCN5/PCAF-dependent acetylation is associated with tumorigenesis and other pathological states, highlighting their importance in maintaining normal cellular function^[2][3]. Compared with the closely related isoform PCAF, GCN5 has been more extensively characterized within distinct SAGA- and ATAC-associated regulatory networks, although both proteins share highly conserved acetyltransferase and bromodomain architectures and exhibit overlapping biological activities^[3][4][7]. Beyond their acetyltransferase function, both GCN5 and PCAF possess ubiquitination activity mediated by the PCAF_N region, indicating additional regulatory mechanisms that extend their influence on protein homeostasis and signaling pathways^[7]. For experimental applications, pharmacological inhibition of GCN5/PCAF acetyltransferase activity, including the use of compounds such as CPTH2, has provided useful approaches for investigating chromatin regulation and acetylation-dependent biological processes^[8].