E1A-binding protein p400-KAT5 complex (p400 complex)

The E1A-binding protein p400-KAT5 complex is a large, multi-subunit molecular machine that functions at the interface of ATP-dependent chromatin remodeling and histone acetylation. As the mammalian ortholog of the yeast NuA4 complex, it plays a critical role in regulating genome accessibility by catalyzing the exchange of histone H2A for the H2A.Z variant and acetylating histones H4 and H2A. These activities are essential for DNA double-strand break repair, transcriptional activation, and cell cycle progression through the regulation of promoters like p21. In clinical contexts, the complex is a significant therapeutic target; its dysregulation is linked to various cancers, including acute myeloid leukemia (AML) and prostate cancer, where it supports oncogenic gene expression and genomic stability. Furthermore, the complex acts as a host restriction factor in HIV-1 infection by promoting viral latency through the suppression of Tat-dependent transcription. Pharmacological modulation typically focuses on inhibiting the KAT5 (TIP60) acetyltransferase subunit, with small-molecule inhibitors being explored for their potential to sensitize cancer cells to DNA-damaging agents or reverse viral latency.

Other names

NuA4 complexTIP60 complexTIP60/p400 complexhTIP60-CEP400 complexKAT5 complexEP400-KAT5 complex

Histone acetyltransferase inhibition