Lysine acetyltransferase 6A (KAT6A) (KAT6A)

Lysine acetyltransferase 6A (KAT6A), also known as MOZ, is a member of the MYST family of histone acetyltransferases that plays a critical role in epigenetic regulation [1, 3, 15]. It functions as part of a multisubunit complex to acetylate lysine residues on histone H3, particularly H3K9, H3K14, and H3K23, thereby promoting an open chromatin structure and activating gene transcription [3, 12, 15]. KAT6A is essential for the maintenance of hematopoietic and neural stem cells and is involved in various developmental processes [1, 3, 4]. In pathology, KAT6A is frequently dysregulated; it is a known oncogene in acute myeloid leukemia (AML) through chromosomal translocations and is amplified in approximately 10-15% of ER-positive breast cancers [4, 7, 14]. In breast cancer, KAT6A regulates the expression of the estrogen receptor (ESR1), and its inhibition has emerged as a promising therapeutic strategy to overcome resistance to endocrine therapies [2, 14]. Clinical-stage inhibitors like prifetrastat (PF-07248144) target the catalytic activity of both KAT6A and its paralog KAT6B, showing potential in treating advanced solid tumors [2, 6, 10]. Therapeutic challenges include managing side effects such as dysgeusia and neutropenia, which have been observed in early clinical trials [10, 14].

Other names

MOZMYST3RUNXBP2ZNF220ZC2HC6AMonocytic leukemia zinc finger proteinLysine acetyltransferase 6BKAT6BMORFMYST4MOZ2KAT6

Inhibition of histone acetyltransferase catalytic activity