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