EP300

E1A binding protein p300 also known as EP300 or p300 is a is_associated_with::protein that, in humans, is encoded by the EP300 is_associated_with::gene. This protein regulates the activity of many genes in tissues throughout the body. It plays an essential role in regulating is_associated_with::cell growth and division, prompting cells to mature and assume specialized functions (differentiate), and preventing the growth of cancerous tumors. The p300 protein appears to be critical for normal development before and after is_associated_with::birth.

The p300 protein carries out its function by activating transcription. To be specific, p300 connects is_associated_with::transcription factors, which are proteins that start the transcription process, with the complex of proteins that carry out transcription in the cell's nucleus. On the basis of this function, p300 is called a transcriptional is_associated_with::coactivator. The p300 interaction with transcription factors is managed by one or more of p300 domains: the is_associated_with::nuclear receptor interaction domain (RID), the is_associated_with::CREB and MYB interaction domain (KIX), the is_associated_with::cysteine/is_associated_with::histidine regions (TAZ1/CH1 and TAZ2/CH3) and the is_associated_with::interferon response binding domain (IBiD). The last four domains, KIX, TAZ1, TAZ2 and IBiD of p300, each bind tightly to a sequence spanning both transactivation domains 9aaTADs of transcription factor p53.

The EP300 gene is located on the long (q) arm of the human chromosome 22 at position 13.2.

EP300 is closely related to another gene, is_associated_with::CREB binding protein, which is found on human chromosome 16.

Function
This gene encodes the is_associated_with::adenovirus E1A-associated cellular p300 transcriptional co-activator protein.

The protein functions as is_associated_with::histone acetyltransferase that regulates transcription via chromatin remodeling, and is important in the processes of cell proliferation and differentiation. It mediates cAMP-gene regulation by binding specifically to phosphorylated is_associated_with::CREB protein.

This gene has also been identified as a co-activator of is_associated_with::HIF1A (hypoxia-inducible factor 1 alpha), and, thus, plays a role in the stimulation of hypoxia-induced genes such as VEGF.

Clinical significance
is_associated_with::Mutations in the EP300 gene are responsible for a small percentage of cases of is_associated_with::Rubinstein-Taybi syndrome. These mutations result in the loss of one copy of the gene in each cell, which reduces the amount of p300 protein by half. Some mutations lead to the production of a very short, nonfunctional version of the 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 p300 protein leads to the specific features of Rubinstein-Taybi syndrome, it is clear that the loss of one copy of the EP300 gene disrupts normal development.

Chromosomal rearrangements involving chromosome 22 have rarely been associated with certain types of is_associated_with::cancer. These rearrangements, called translocations, disrupt the region of chromosome 22 that contains the EP300 gene. For example, researchers have found a translocation between chromosomes 8 and 22 in several people with a cancer of blood cells called is_associated_with::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 EP300 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 EP300 gene have been found in a small number of solid tumors, including cancers of the colon and is_associated_with::rectum, is_associated_with::stomach, is_associated_with::breast, and is_associated_with::pancreas. Studies suggest that EP300 mutations may also play a role in the development of some is_associated_with::prostate cancers, and could help predict whether these tumors will increase in size or spread to other parts of the body. In cancer cells, EP300 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.

Interactions
EP300 has been shown to interact with:


 * is_associated_with::BCL3,
 * is_associated_with::BRCA1,
 * is_associated_with::CDX2,
 * is_associated_with::CEBPB,
 * is_associated_with::CITED1,
 * is_associated_with::CITED2,
 * is_associated_with::DDX5,
 * is_associated_with::DTX1,
 * is_associated_with::EID1,
 * is_associated_with::ELK1,
 * ESR1,
 * FEN1,
 * GPS2,
 * is_associated_with::HIF1A,
 * is_associated_with::HNF1A,
 * is_associated_with::HNRPU,
 * is_associated_with::ING4,
 * is_associated_with::ING5,
 * is_associated_with::IRF2,
 * LEF1,
 * MAF,
 * is_associated_with::MAML1,
 * is_associated_with::MEF2C,
 * is_associated_with::MEF2D,
 * is_associated_with::MYBL2,
 * is_associated_with::Mdm2,
 * is_associated_with::MyoD,
 * MEF2A,
 * is_associated_with::NCOA6,
 * is_associated_with::NFATC2,
 * is_associated_with::NPAS2,
 * is_associated_with::P53,
 * is_associated_with::PAX6,
 * is_associated_with::PCNA,
 * is_associated_with::PROX1,
 * is_associated_with::PTMA,
 * PPARA,
 * PPARG,
 * RORA,
 * is_associated_with::RELA,
 * SMAD1,
 * SMAD2,
 * SMAD7,
 * is_associated_with::SNIP1,
 * is_associated_with::SS18,
 * is_associated_with::STAT3,
 * is_associated_with::STAT6,
 * is_associated_with::TAL1,
 * is_associated_with::TCF3,
 * is_associated_with::TFAP2A,
 * is_associated_with::TGS1,
 * is_associated_with::TRERF1,
 * is_associated_with::TSG101,
 * THRA,
 * TWIST1,
 * is_associated_with::YY1,  and
 * is_associated_with::Zif268.