[HTML][HTML] Protein lysine acetylation by p300/CBP

BM Dancy, PA Cole - Chemical reviews, 2015 - ACS Publications
Chemical reviews, 2015ACS Publications
Since their discovery in the 1980s and 1990s, the human protein lysine acetyltransferase
encoded by the paralogous p300 and CBP genes has received much interest. p300/CBP
functions in regulating the expression of genes controlling several basic cellular processes,
such as proliferation and homeostasis, and plays a role in a variety of human diseases,
particularly solid tumors. Numerous natural product and synthetic inhibitors of the
acetyltransferase activity have been identified and used to generate a crystal structure of the …
Since their discovery in the 1980s and 1990s, the human protein lysine acetyltransferase encoded by the paralogous p300 and CBP genes has received much interest. p300/CBP functions in regulating the expression of genes controlling several basic cellular processes, such as proliferation and homeostasis, and plays a role in a variety of human diseases, particularly solid tumors.
Numerous natural product and synthetic inhibitors of the acetyltransferase activity have been identified and used to generate a crystal structure of the active site, probe the p300/CBP enzyme kinetics, and interrogate p300/CBP cellular functions. These studies revealed that acetyl-CoA binds in a tunnel enclosed by a unique loop, while the substrate protein transiently associates with an acidic patch, following a hit-andrun kinetic mechanism. p300/CBP acetylates histones as well as other proteins including other epigenetic enzymes and transcription factors. Studies with inhibitor compounds in cells and animals have confirmed that the p300/CBP acetylation activity has roles in diverse functions including cell migration and invasion, maintenance of the differentiated state, tau-mediated neurodegeneration, and learning and memory.
ACS Publications