CREB-binding protein (CBP) (CBP)

CREB-binding protein (CBP), also known as KAT3A, is a large, multidomain transcriptional coactivator that plays a pivotal role in eukaryotic gene expression by integrating signals from various transcription factors [1, 2]. It possesses intrinsic histone acetyltransferase (HAT) activity, which catalyzes the transfer of an acetyl group to lysine residues on histones H3 and H4, thereby relaxing chromatin structure and facilitating transcriptional activation [1, 3]. CBP is highly homologous to p300 (EP300), and together they function as central nodes in cellular signaling pathways, regulating processes such as cell growth, differentiation, and the DNA damage response [2, 5]. In human disease, CBP is frequently implicated in oncogenesis through gene fusions, deletions, or point mutations, particularly in hematological malignancies and solid tumors like prostate cancer [1, 4]. Therapeutic targeting of CBP has focused on small molecule inhibitors of its HAT domain to block catalytic activity or its bromodomain to prevent recruitment to acetylated chromatin [3, 5]. Clinical-stage candidates like CCS1477 (Inobrodib) are being evaluated for their ability to downregulate oncogenic drivers, such as the androgen receptor and MYC, in treatment-resistant cancers [4].

Other names

CREBBPKAT3AHistone acetyltransferase CBPRubinstein-Taybi syndrome proteinRSTSRTS

Inhibition of the histone acetyltransferase (HAT) catalytic domain or the bromodomain to disrupt transcriptional coactivation and chromatin modification.