Post-translational modifications of epigenetic modifier TIP60: their role in cellular functions and cancer

TIP60 is a crucial lysine acetyltransferase protein that catalyzes the acetylation of histone and non-histone proteins. This enzyme plays a crucial role in maintaining genomic integrity, by participating in DNA damage repair, ensuring accurate chromosomal segregation, and regulating a myriad of cellular processes such as apoptosis, autophagy, and wound-induced cell migration. One of the primary mechanisms through which TIP60 executes these diverse cellular functions is via post-translational modifications (PTMs). Over the years, extensive studies have demonstrated the importance of PTMs in controlling protein functions. This review aims to summarize the findings on PTMs occurring on the TIP60 protein and their functional implications. We also discuss previously uncharacterized PTM sites identified on TIP60 and examine their relationship with cancer-associated mutations, with a particular focus on residues potentially modified by various PTMs, to understand the cause of deregulation of TIP60 in various cancers.