p300-CBP coactivator family – clinical significance
Mutations in CBP, and to a lesser extent p300, are the cause of Rubinstein-Taybi Syndrome, which is characterized by severe mental retardation. These mutations result in the loss of one copy of the gene in each cell, which reduces the amount of CBP or p300 protein by half. Some mutations lead to the production of a very short, nonfunctional version of the CBP or p300 protein, while others prevent one copy of the gene from making any protein at all. Although researchers do not know how a reduction in the amount of CBP or p300 protein leads to the specific features of Rubinstein-Taybi syndrome, it is clear that the loss of one copy of the CBP or p300 gene disrupts normal development.
Petrij F, Giles RH, Dauwerse HG, Saris JJ, Hennekam RC, Masuno M, Tommerup N, van Ommen GJ, Goodman RH, Peters DJ (Jul 1995). “Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP”. Nature. 376 (6538): 348–51. Bibcode:1995Natur.376..348P. doi:10.1038/376348a0. PMID7630403. S2CID4254507.
Defects in CBP HAT activity appears to cause problems in long-term memory formation.
CBP and p300 have also been found to be involved in multiple rare chromosomal translocations that are associated with acute myeloid leukemia. For example, researchers have found a translocation between chromosomes 8 and 22 (in the region containing the p300 gene) in several people with a cancer of blood cells called acute myeloid leukemia (AML). Another translocation, involving chromosomes 11 and 22, has been found in a small number of people who have undergone cancer treatment. This chromosomal change is associated with the development of AML following chemotherapy for other forms of cancer.
Mutations in the p300 gene have been identified in several other types of cancer. These mutations are somatic, which means they are acquired during a person’s lifetime and are present only in certain cells. Somatic mutations in the p300 gene have been found in a small number of solid tumors, including cancers of the colon and rectum, stomach, breast and pancreas. Studies suggest that p300 mutations may also play a role in the development of some prostate cancers, and could help predict whether these tumors will increase in size or spread to other parts of the body. In cancer cells, p300 mutations prevent the gene from producing any functional protein. Without p300, cells cannot effectively restrain growth and division, which can allow cancerous tumors to form.
