CBPp300

CBPp300 refers to the CREB-binding protein (CBP) and its closely related paralog p300, two large nuclear transcriptional coactivators in humans encoded by CREBBP and EP300. They function primarily as histone acetyltransferases and scaffolds that link sequence-specific transcription factors to the transcriptional machinery, thereby regulating gene expression in many cell types.

Both proteins are approximately 2,400 amino acids in length and share substantial sequence similarity. Their modular structure includes an N-terminal region with transcription factor interaction domains such as KIX and CH motifs, a central histone acetyltransferase (HAT) catalytic domain, a bromodomain to recognize acetylated lysines, and multiple activation domains that recruit other coactivators and RNA polymerase II.

Functionally, CBP and p300 acetylate histone tails, notably H3 and H4, to loosen chromatin and promote transcription. They also acetylate a range of non-histone substrates, including transcription factors and chromatin remodelers, modulating their activity. As scaffolds, they integrate signals from diverse pathways (for example CREB, NF-κB, and MYB) and help recruit components of the basal transcription machinery.

Biological roles of CBP/p300 span development, differentiation, learning and memory, and the DNA damage response. They influence stem cell pluripotency and cell-cycle regulation and are broadly required for normal embryogenesis in model systems.

Clinical significance includes Rubinstein-Taybi syndrome, caused by germline mutations in CREBBP or EP300, which leads to features such as broad thumbs, facial characteristics, growth retardation, and cognitive impairment. Somatic alterations of these genes occur in several cancers, contributing to oncogenesis in some contexts. Because of their central role in transcription, CBP/p300 are targets of therapeutic inhibitors aimed at the HAT domain or bromodomain, under investigation as anticancer strategies.