The PCAF gene is mapped to human chromosome 3p24.3.
p300/CBP-associated factor (PCAF) is a member of the histone acetyltransferases (HATs) protein family. It is also known as KAT2B (lysine acetyltransferase 2B), and is the catalytic subunit of the megadalton metazoan complex ATAC (Ada-Two-A containing complex). In animals, this protein is composed of an N terminal extension region, a HAT domain and a bromodomain (BRD). An acetyl-CoA binding pocket is present in the HAT domain, which is globular in structure. This protein is composed of over 2400 amino acids.
p300/CBP-associated factor (PCAF) protein functions as a co-activator of the tumor suppressor gene p53, and transactivates target genes along with p53, by acetylating both bound p53 and histones within p53 target promoters. Studies in breast cancer cells show that PCAF is a p53 target gene, and its induction results in increased p53 binding to PCAF promoter. This protein interacts with multiple DNA-binding transcriptional factors, such as nuclear hormone receptors, CREB (cAMP response element-binding, c-Jun/v-Jun, c-Myb/v-Myb, Sap-1a, c-Fos, and MyoD (myogenic differentiation).
PCAF belongs to the GCN5/PCAF family of nuclear HATs. The proteins consist of N-terminal and C-terminal domains separated by a deep hydrophobic cleft. The C-terminus contains the HAT domain and a bromodomain, while the N-terminus contains a PCAF-specific domain. CBP and p300 are large nuclear proteins that bind to many sequence-specific factors involved in cell growth and/or differentiation, including c-jun and the adenoviral oncoprotein E1A. The protein encoded by this gene associates with p300/CBP. It has in vitro and in vivo binding activity with CBP and p300, and competes with E1A for binding sites in p300/CBP. Numerous studies indicate that these HATs function as histone- acetylating transcriptional co-activators. Besides histones, PCAF also acetylates non-histone proteins. It has histone acetyl transferase activity with core histones and nucleosome core particles, indicating that this protein plays a direct role in transcriptional regulation.
PCAF brings about the differentiation of mesenchymal stem cells into bone tissues. PCAF competes with E1A for binding to P300/CBP and inhibit cellular transformation. The gene is downregulated in hepatocellular carcinoma and is found to be associated with tumor metastasis.