Transformation/transcription domain-associated protein

Transformation/transcription domain-associated protein, also known asTRRAP, is a is_associated_with::protein that in humans is encoded by the TRRAP is_associated_with::gene. TRRAP belongs to the is_associated_with::phosphatidylinositol 3-kinase-related kinase protein family.

Function
TRRAP is an is_associated_with::adapter protein, which is found in various multiprotein is_associated_with::chromatin complexes with is_associated_with::histone acetyltransferase activity (HAT), which in turn is responsible for is_associated_with::epigenetic transcription activation. TRRAP has a central role in is_associated_with::MYC (c-Myc) transcription activation, and also participates in cell transformation by MYC. It is required for p53/is_associated_with::TP53-, is_associated_with::E2F1-, and is_associated_with::E2F4-mediated transcription activation. It is also involved in transcription activation mediated by the is_associated_with::adenovirus E1A, a viral is_associated_with::oncoprotein that deregulates transcription of key genes.

TRRAP is also required for the mitotic checkpoint and normal is_associated_with::cell cycle progression. The MRN complex (composed of MRE11, RAD50, and NBS1) is involved in the detection and repair of DNA double-strand breaks (DSBs). TRRAP associates with the MRN complex and when TRRAP is removed, the complex shows reduced cDNA end-joining activity. Hence, TRRAP may function as a link between DSB repair and chromatin remodeling.

Model organisms
is_associated_with::Model organisms have been used in the study of TRRAP function. A conditional is_associated_with::knockout mouse line, called Trraptm1a(EUCOMM)Wtsi was generated as part of the is_associated_with::International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.

Male and female animals underwent a standardized is_associated_with::phenotypic screen to determine the effects of deletion. Twenty four tests were carried out on is_associated_with::mutant mice and two significant abnormalities were observed. No is_associated_with::homozygous is_associated_with::mutant embryos were identified during gestation, and therefore none survived until is_associated_with::weaning. The remaining tests were carried out on is_associated_with::heterozygous mutant adult mice; no significant abnormalities were observed in these animals.

Interactions
Transformation/transcription domain-associated protein has been shown to interact with:
 * is_associated_with::ACTL6A,
 * is_associated_with::EP400,
 * MAX,
 * is_associated_with::Myc,
 * is_associated_with::PCAF,
 * SUPT3H, and
 * is_associated_with::TAF9. and