CBP has intrinsic acetyltransferase functions

Cyclic adenosine monophosphate Response Element Binding protein Binding Protein (CREB-binding protein), also known as CREBBP or CBP or KAT3A, is a coactivator encoded by the CREBBP gene in humans, located on chromosome 16p13.3.

• Chan HM, La Thangue NB (July 2001). “p300/CBP proteins: HATs for transcriptional bridges and scaffolds”. Journal of Cell Science. 114 (Pt 13): 2363–2373. doi:10.1242/jcs.114.13.2363. PMID 11559745.
• Yao W, Wang T, Huang F (2018). “p300/CBP as a Key Nutritional Sensor for Hepatic Energy Homeostasis and Liver Fibrosis”. BioMed Research International. 2018: 8168791. doi:10.1155/2018/8168791. PMC 5976926. PMID 29862292.

CBP has intrinsic acetyltransferase functions; it is able to add acetyl groups to both transcription factors as well as histone lysines, the latter of which has been shown to alter chromatin structure making genes more accessible for transcription.

• Vo N, Goodman RH (April 2001). “CREB-binding protein and p300 in transcriptional regulation”. The Journal of Biological Chemistry. 276 (17): 13505–13508. doi:10.1074/jbc.R000025200. PMID 11279224.
• Akinsiku OE, Soremekun OS, Soliman ME (February 2021). “Update and Potential Opportunities in CBP [Cyclic Adenosine Monophosphate (cAMP) Response Element-Binding Protein (CREB)-Binding Protein] Research Using Computational Techniques”. The Protein Journal. 40 (1): 19–27. doi:10.1007/s10930-020-09951-8. PMC 7868315. PMID 33394237.
• Guo P, Chen W, Li H, Li M, Li L (October 2018). “The Histone Acetylation Modifications of Breast Cancer and their Therapeutic Implications”. Pathology & Oncology Research. 24 (4): 807–813. doi:10.1007/s12253-018-0433-5. PMID 29948617. S2CID 47020435.
• He ZX, Wei BF, Zhang X, Gong YP, Ma LY, Zhao W (January 2021). “Current development of CBP/p300 inhibitors in the last decade”. European Journal of Medicinal Chemistry. 209: 112861. doi:10.1016/j.ejmech.2020.112861. ISSN 0223-5234. PMID 33045661. S2CID 222319204.

This relatively unique acetyltransferase activity is also seen in another transcription enzyme, EP300 (p300). Together, they are known as the p300-CBP coactivator family and are known to associate with more than 16,000 genes in humans; however, while these proteins share many structural features, emerging evidence suggests that these two co-activators may promote transcription of genes with different biological functions.

• Vo N, Goodman RH (April 2001). “CREB-binding protein and p300 in transcriptional regulation”. The Journal of Biological Chemistry. 276 (17): 13505–13508. doi:10.1074/jbc.R000025200. PMID 11279224.
• Bordonaro M, Lazarova DL (July 2015). “CREB-binding protein, p300, butyrate, and Wnt signaling in colorectal cancer”. World Journal of Gastroenterology. 21 (27): 8238–8248. doi:10.3748/wjg.v21.i27.8238. PMC 4507093. PMID 26217075.
• Attar N, Kurdistani SK (March 2017). “Exploitation of EP300 and CREBBP Lysine Acetyltransferases by Cancer”. Cold Spring Harbor Perspectives in Medicine. 7 (3): a026534. doi:10.1101/cshperspect.a026534. PMC 5334244. PMID 27881443.

For example, CBP alone has been implicated in a wide variety of pathophysiologies including colorectal cancer as well as head and neck squamous cell carcinoma. In these diseases, association of CBP with β-catenin has been shown to promote cancer cell proliferation and disease aggressiveness, whereas p300/ β-catenin leads to cell differentiation and/ or apoptosis.

• Bordonaro M, Lazarova DL (July 2015). “CREB-binding protein, p300, butyrate, and Wnt signaling in colorectal cancer”. World Journal of Gastroenterology. 21 (27): 8238–8248. doi:10.3748/wjg.v21.i27.8238. PMC 4507093. PMID 26217075
• Kartha VK, Alamoud KA, Sadykov K, Nguyen BC, Laroche F, Feng H, et al. (July 2018). “Functional and genomic analyses reveal therapeutic potential of targeting β-catenin/CBP activity in head and neck cancer”. Genome Medicine. 10 (1): 54. doi:10.1186/s13073-018-0569-7. PMC 6053793. PMID 30029671.

CBP has also been shown to help modulate liver function via maintenance of energy homeostasis in response to changes in cell nutrition conditions by regulating the activity of transcription factors and genes responsible for lipogenesis and gluconeogenesis.

• Yao W, Wang T, Huang F (2018). “p300/CBP as a Key Nutritional Sensor for Hepatic Energy Homeostasis and Liver Fibrosis”. BioMed Research International. 2018: 8168791. doi:10.1155/2018/8168791. PMC 5976926. PMID 29862292.

CBP is also implicated in the etiologies of several other diseases including hematologic malignancies and other solid tumors, diabetes, schizophrenia, Alzheimer’s Disease, depression, and many other neurological conditions.

• Rouaux C, Loeffler JP, Boutillier AL (September 2004). “Targeting CREB-binding protein (CBP) loss of function as a therapeutic strategy in neurological disorders”. Biochemical Pharmacology. 68 (6): 1157–1164. doi:10.1016/j.bcp.2004.05.035. PMID 15313413.
• Wang H, Xu J, Lazarovici P, Quirion R, Zheng W (2018-08-30). “cAMP Response Element-Binding Protein (CREB): A Possible Signaling Molecule Link in the Pathophysiology of Schizophrenia”. Frontiers in Molecular Neuroscience. 11: 255. doi:10.3389/fnmol.2018.00255. PMC 6125665. PMID 30214393.
• Amidfar M, de Oliveira J, Kucharska E, Budni J, Kim YK (September 2020). “The role of CREB and BDNF in neurobiology and treatment of Alzheimer’s disease”. Life Sciences. 257: 118020. doi:10.1016/j.lfs.2020.118020. PMID 32603820. S2CID 220287306.
• Steven A, Friedrich M, Jank P, Heimer N, Budczies J, Denkert C, Seliger B (October 2020). “What turns CREB on? And off? And why does it matter?”. Cellular and Molecular Life Sciences. 77 (20): 4049–4067. doi:10.1007/s00018-020-03525-8. PMC 7532970. PMID 32347317.
• Dutta R, Tiu B, Sakamoto KM (September 2016). “CBP/p300 acetyltransferase activity in hematologic malignancies”. Molecular Genetics and Metabolism. 119 (1–2): 37–43. doi:10.1016/j.ymgme.2016.06.013. PMID 27380996.