The versatile functions of the transcriptional coactivators p300 and CBP and their roles in disease

Abstract

p300 and CBP are highly homologous c o a c t ivators which promote gene transcription by bridging between DNA-binding transcription factors and the basal transcription machinery, by providing a s c a ffold for integrating transcription factors, and by modifying transcription factors and chromatin through acetylation. The p300/CBP cofactors are invo l ved in a plethora of physiological processes, and their activity is essential for embryogenesis. Chromosomal translocations affecting the p300 and Cbp genes are the cause of hematological malignancies, and C b p haploinsufficiency is a hallmark of the Rubinstein-Taybi syndrome. In addition, mutations in the C b p or p 3 0 0 gene, accompanied by loss of the other allele, have been found in various kinds of tumors. Furthermore, inhibition of CBP and p300 function in n e u r o d eg e n e r a t ive diseases caused by polyglutamine expansion may be an underlying cause for cytotoxicity. Approaches to modulate p300/CBP function may be instrumental in the development of novel therapies directed against viral infections, cancer and neurodegenerative diseases.