TRRAP, also known as transformation/transcription domain-associated protein, which is a protein encoded by the TRRAP gene in humans. TRRAP belongs to the family of phosphatidylinositol 3-kinase-related kinase proteins.

Functions

TRRAP is an adaptor protein that exists in multiple polyprotein chromatin complexes with histone acetyltransferase activity (HAT), which is responsible for epigenetic transcriptional activation. TRRAP plays a central role in MYC (c-Myc) transcriptional activation and is also involved in MYC cell transformation. It is required for p53/TP53-, E2F1-, and E2F4-mediated transcriptional activation. It is also involved in transcriptional activation mediated by adenovirus E1A, a viral oncoprotein that regulates the transcription of key genes. TRRAP is also required for mitotic checkpoints 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 (DSB). TRRAP is associated with the MRN complex, and when TRRAP is removed, the complex shows reduced cDNA end-ligating activity. Therefore, TRRAP may serve as a link between DSB repair and chromatin remodeling.

Introductions about adaptor protein

Signal transduction adaptor protein (STAP) is a helper protein for major proteins in the signal transduction pathway. Adaptor proteins contain a variety of protein-binding modules that connect protein-binding partners together and help create larger signaling complexes. These proteins often lack any inherent enzymatic activity, but rather mediate specific protein-protein interactions that drive the formation of protein complexes. Adaptor proteins often contain several domains within their structure (eg, Src homology 2 (SH2) and SH3 domains), which allow specific interactions with several other specific proteins. The SH2 domain recognizes specific amino acid sequences within proteins containing phosphotyrosine residues, while the SH3 domain recognizes proline-rich sequences within specific peptide sequences of proteins. Many other types of interaction domains have been found in adaptors and other signaling proteins. These interaction domains allow a variety of specific and cooperative protein interactions to occur within the cell during signal transduction.

Figure 1. Protein structure of adaptor protein.

Applications

Model organisms have been used to study the function of TRRAP. A conditional knockout mouse line, called Traraptm, is part of the International Knockout Mouse Association program, a high-throughput mutagenesis project designed to generate and distribute animal models of disease to Interested scientist. Male and female animals were subjected to standardized phenotypic screening to determine the effects of deletions. Twenty-four tests were performed on mutant mice and two distinct abnormalities were observed. No homozygous mutant embryos were identified during pregnancy and therefore did not survive until weaning. The remaining tests were performed on heterozygous adult mice. No significant abnormalities were observed in these animals.

References

1. Takaesu G; et al. TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway. Molecular Cell, 2000, 5(4):649-658.
2. Robert F; et al. The Transcriptional Histone Acetyltransferase Cofactor TRRAP Associates with the MRN Repair Complex and Plays a Role in DNA Double-Strand Break Repair. Mol. Cell. Biol. 2006, 26 (2): 402-12.