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

CREB-binding protein (CREBBP/CBP) and E1A-binding protein p300 (EP300/p300) are highly homologous paralogous proteins that function as essential transcriptional coactivators and lysine acetyltransferases (KATs) [3, 9]. They play a pivotal role in chromatin remodeling by acetylating histones, particularly H3K18 and H3K27, which promotes an open chromatin state and facilitates gene transcription [4, 12]. Beyond histones, they acetylate a vast array of non-histone proteins, including transcription factors like p53, GATA1, and the androgen receptor, making them central hubs in cellular signaling and gene regulation [1, 6, 13]. In human disease, CREBBP and EP300 are frequently implicated in both hematological malignancies and solid tumors, where they can function as either tumor suppressors or oncogenes depending on the context [6, 9, 14]. For example, loss-of-function mutations are prevalent in follicular lymphoma and diffuse large B-cell lymphoma, while their coactivator activity is often hijacked in prostate and breast cancers to drive oncogenic programs [2, 8, 14]. Therapeutic targeting of these proteins has focused on small-molecule inhibitors of their catalytic acetyltransferase (HAT) domain or their bromodomain, which recognizes acetylated lysines [4, 6, 14]. Several of these inhibitors, such as CCS1477 and FT-7051, are currently undergoing clinical evaluation for the treatment of advanced cancers [6, 14].

Other names

CREBBPEP300CBPp300KAT3AKAT3BRSTSRSTS1RSTS2

Bromodomain inhibition, histone acetyltransferase (HAT) inhibition, and protein-protein interaction inhibition (e.g., CBP/beta-catenin interaction).