p300CBP

p300CBP, or p300/CBP, refers to two closely related transcriptional coactivators, p300 and CBP, encoded by the genes EP300 and CREBBP. They function as histone acetyltransferases and as scaffolds that coordinate transcriptional activation and chromatin remodeling across numerous signaling pathways. Both proteins are ubiquitously expressed and share substantial sequence similarity, enabling partly overlapping roles in gene regulation.

Biochemical features include a histone acetyltransferase (HAT) domain that acetylates histone and non-histone substrates, a bromodomain that recognizes acetylated lysines, and interaction motifs such as the KIX domain that binds transcription factors. Through these domains, p300/CBP interact with a broad set of transcription factors, including CREB, p53, NF-κB, and nuclear receptors, bridging them to the general transcription machinery.

They promote transcription by remodeling chromatin to a more open state and by acetylating non-histone proteins that control transcription. They influence promoter and enhancer activity, respond to cellular signals, and help recruit RNA polymerase II and coactivator complexes.

Loss or reduced function of either paralog in humans causes Rubinstein–Taybi syndrome when germline mutations occur in CREBBP or EP300, with features such as broad thumbs, facial traits, and developmental delay. Somatic mutations and copy-number alterations in EP300 or CREBBP occur in various cancers; effects are context-dependent and may reflect altered transcriptional programs rather than simple loss of function.

Because of their central role in transcriptional control, CBP/p300 are active areas of drug development. Inhibitors targeting the bromodomain or HAT domain of CBP/p300—such as bromodomain inhibitors and the HAT-domain inhibitor A-485—are under investigation for research and therapeutic potential in cancer and other diseases.