P300/CBP

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It has been suggested that EP300 be merged into this article or section. (Discuss)

E1A binding protein p300
Identifiers
Symbol	EP300
HUGO	3373
Entrez	2033
OMIM	602700
RefSeq	NM_001429
UniProt	Q09472
Other data
Locus	Chr. 22 q13.2

CREB binding protein (Rubinstein-Taybi syndrome)
Identifiers
Symbol	CREBBP RSTS
HUGO	2348
Entrez	1387
OMIM	600140
RefSeq	NM_004380
UniProt	Q92793
Other data
Locus	Chr. 16 p13.3

p300 (also EP300 or E1A binding protein p300) and CBP (also CREBBP or CREB binding protein) are two closely related transcriptional co-activating proteins (or coactivators). p300 and CBP interact with numerous transcription factors and act to increase the expression of their target genes.^[1]^[2]

1 Protein structure
2 Impact on gene expression
3 Function in G protein signaling
4 Clinical significance
5 References
6 External links

[edit] Protein structure

p300 and CBP have similar structures. Both contain five protein interaction domains, the nuclear receptor interaction domain (RID), the CREB and MYB interaction domain (KIX), the cysteine/histidine regions (CH1 and CH3) and the interferon response binding domain (IBiD). In addition p300 and CBP each contain a protein or histone acetyltransferase (PAT/HAT) domain and a bromodomain that binds acetylated lysines.^[3]

[edit] Impact on gene expression

p300 and CBP are thought to increase gene expression in three ways:

1) by relaxing the chromatin structure at the gene promoter through their intrinsic histone acetyltransferase (HAT) activity.
2) recruiting the basal transcriptional machinery including RNA polymerase II to the promoter.
3) acting as adaptor molecules.^[4]

[edit] Function in G protein signaling

An example of a process involving p300 and CBP is G protein signaling. G proteins, such as PKA, consist of four subunits, two regulatory and two catalytic. Binding of cAMP to the regulatory subunits causes release of the catalytic subunits. These subunits can then enter the nucleus to interact with transcriptional factors, thus affecting gene transcription. The transcription factor CREB, which interacts with a DNA sequence called a cAMP response element (or CRE), is phosphorylated by PKA on a serine in the KID domain. This modification promotes the interaction of the KID domain of CREB with the KIX domain of CBP or p300 and enhances transcription of CREB target genes, including genes that aid gluconeogenesis. This pathway is initiated by adrenaline binding to the cell of interest.^[5]

[edit] Clinical significance

Mutations in CBP, and to a lesser extent p300, are associated with Rubinstein-Taybi Syndrome, which is characterized by severe mental retardation. Defects in CBP HAT activity appears to cause problems in long-term memory formation.^[6] CBP and p300 have also been found to be involved in multiple chromosomal translocations that are associated with acute myeloid leukemia.^[7]