Human Tip60 (NuA4) Complex and Cancer

Abstract

Recent publications implicate human Tip60 (NuA4) complex in colorectal and other cancers. Our lab and others discovered deregulations in the components of human Tip60 (NuA4) complex in advanced colon cancers, and the functional significance and the potential as a therapeutic target, has been investigated. Human Tip60 (NuA4) complex likely represents a fusion form of yeast NuA4 and SWR1 complexes, and the functions seem to be evolutionarily preserved. This notion has greatly contributed in understanding functions of human Tip60 (NuA4) complex. The Tip60 (NuA4) complex is a multiprotein complex with at least 16 subunits. It is thought to function in at least two ways; (a) as a chromatin remodeling factor, it controls chromatin structure and transcription through its Histone Acetyl Transferase (HAT) activity, and (b) it controls activities of other nonhistone proteins, such as metabolic enzymes, through protein acetylation. Through the enzymatic activity and other interactions, Tip60 (NuA4) complex is involved in wide variety of cellular functions, including transcriptional activation, DNA repair, cell cycle progression, chromosome stability, stem cell maintenance and differentiation, and cell migration and invasion. This review will discuss functions of Tip60 (NuA4) complex, consequences of the defect in the subunit, its connection to human cancer, and its potential as a therapeutic target in clinic.