Transformation/transcription domain-associated protein

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

Function

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

TRRAP is also required for the mitotic checkpoint and normal 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

Trrap knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Abnormal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma immunoglobulins	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Brain histopathology	Normal
Salmonella infection	Normal
Citrobacter infection	Normal
All tests and analysis from

Model organisms have been used in the study of TRRAP function. A conditional knockout mouse line, called Trrap^{tm1a(EUCOMM)Wtsi} was generated as part of the 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 phenotypic screen to determine the effects of deletion. Twenty four tests were carried out on mutant mice and two significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no significant abnormalities were observed in these animals.

Interactions

Transformation/transcription domain-associated protein has been shown to interact with:

• ACTL6A,
• EP400,
• MAX,
• Myc,
• PCAF,
• SUPT3H, and
• TAF9. and