E1A-binding protein p300 and CREB-binding protein (p300/CBP)

E1A-binding protein p300 and CREB-binding protein (CBP), collectively known as p300/CBP, are highly homologous paralogous enzymes that function as essential transcriptional coactivators and histone acetyltransferases (HATs). They act as molecular hubs in cellular signaling, interacting with hundreds of transcription factors to regulate gene expression through the acetylation of lysine residues on both histones and non-histone proteins. This modification leads to the relaxation of chromatin structure, facilitating the recruitment of the transcriptional machinery and the activation of target genes involved in cell growth, differentiation, and development. In cancer, p300/CBP are frequently dysregulated or overexpressed, where they drive the expression of oncogenic programs such as those mediated by the androgen receptor (AR) in prostate cancer or c-MYC in hematological malignancies. Therapeutic strategies targeting p300/CBP include small-molecule inhibitors of the HAT domain or the bromodomain, as well as proteolysis-targeting chimeras (PROTACs) designed to induce their degradation. These agents aim to suppress oncogene transcription and induce tumor cell death, although their broad regulatory functions necessitate careful management of potential toxicities in normal tissues.

Other names

EP300CREBBPp300CBPKAT3AKAT3BHistone acetyltransferase p300CREB-binding proteinE1A-associated protein p300

Inhibition of the histone acetyltransferase (HAT) catalytic activity, competitive inhibition of the bromodomain (BD) reader function to prevent chromatin binding, or targeted proteasomal degradation using PROTAC technology.