Lysine acetyltransferase 2A and Lysine acetyltransferase 2B (KAT2A and KAT2B)

Lysine acetyltransferase 2A (KAT2A, also known as GCN5) and Lysine acetyltransferase 2B (KAT2B, also known as PCAF) are closely related histone acetyltransferases that catalyze the transfer of acetyl groups from acetyl-CoA to specific lysine residues on histone H3, promoting an open chromatin state and activating gene transcription. KAT2A and KAT2B also function in multi-protein complexes (SAGA, ATAC) and regulate non-histone proteins involved in cell fate decisions and signal transduction pathways. Both play key roles in stem cell maintenance, differentiation, development (including craniofacial patterning), immune cell maturation, and neural plasticity. Overexpression or altered function of these enzymes is linked to cancer aggressiveness, while their genetic depletion impairs cellular proliferation, self-renewal, and differentiation, making them potential but challenging therapeutic targets. Their activity is required for normal developmental, homeostatic, and memory functions, so pharmacological targeting may involve significant safety challenges.

Other names

KAT2A (formerly GCN5, General control non-derepressible 5)KAT2B (formerly PCAF, p300/CBP-associated factor)Histone acetyltransferase GCN5Histone acetyltransferase PCAFGCN5L2 (for KAT2A)PCAF (for KAT2B)

Inhibition of KAT2A/KAT2B blocks histone acetylation (primarily at H3K9 and H3K14), leading to chromatin condensation and repression of gene transcription. Drugs acting on these enzymes can reduce tumor cell proliferation and stemness, and promote differentiation in cancer models. Disruption may alter differentiation and maintenance of stem cells. Possible influence on non-histone protein acetylation affecting cell signaling and survival.