Acetyltransferases and tumour suppression

Post-translational modifications have long been recognised as important in the regulation of protein function and, until recently, phosphorylation has received the most interest and attention. Over the past few years, however, an appreciation of the role of protein acetylation has increased rapidly, with suggestions that it may rival phosphorylation as a critical regulatory modification [1]. CBP and p300 are two closely related proteins that function to acetylate target proteins, and they can form interactions with a growing list of cellular proteins, including transcription factors that play important roles in the regulation of cell growth, such as c-jun, E2F-1, p53, and NF-κ B [2]. Although CBP and p300 have been postulated to function as tumour suppressors, unequivocal evidence from human malignancies has been lacking. A recent report by Gayther et al [3] takes a significant step in rectifying this deficiency, with the identification of truncating mutations of p300 being associated with mutation of the second allele in both tumour samples and cell lines.Both CBP and p300 are histone acetyltransferases (HATs) [4,5], as are a number of other transcriptional coactivators, including TAF250 and P/CAF [6,7]. One mechanism through which these HATs are thought to regulate transcription is the modulation of chromatin structure, via acetylation of histones, which relaxes the interaction of histones with DNA. The acetylases can form a bridge between transcription factors and the basal transcription machinery [2], therefore enhancing transcriptional activation. Since CBP and p300 are present at limiting concentrations within cells, competition for them between different transcription factors can facilitate integration of different signal transduction pathways [8,9]. Although the acetylation of histones is an important property of CBP and p300, in terms of mediating transcriptional activation, there is growing evidence for the importance of acetylation of other protein target