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Gene Review

TRRAP  -  transformation/transcription domain...

Homo sapiens

Synonyms: 350/400 kDa PCAF-associated factor, PAF350/400, PAF400, STAF40, TR-AP, ...
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Disease relevance of TRRAP


High impact information on TRRAP

  • TRRAP also interacts specifically with the E2F-1 transactivation domain [4].
  • Expression of transdominant mutants of the TRRAP protein or antisense RNA blocks c-Myc- and E1A-mediated oncogenic transformation [4].
  • Chromatin-immunoprecipitation experiments demonstrate that the Gal4-Tra1 interaction is required for recruitment of SAGA to the upstream activating sequence (UAS), and SAGA, in turn, recruits the Mediator complex to the UAS [5].
  • Down-regulation of cyclin D2 mRNA expression in differentiating HL60 cells is preceded by a switch of promoter occupancy from Myc/Max to Mad/Max complexes, loss of TRRAP binding, increased HDAC1 binding, and histone deacetylation [6].
  • Binding of Myc induces cyclin D2 expression and histone acetylation at a single nucleosome in a MycBoxII/TRRAP-dependent manner [6].

Biological context of TRRAP


Anatomical context of TRRAP

  • However, recruitment of TRRAP by c- or N-Myc is dispensable for the partial induction of several basally expressed genes in exponentially growing primary and immortalized fibroblasts [9].
  • We previously isolated the TRRAP/TIP60 complex from HeLa cells (Cai, Y., Jin, J., Tomomori-Sato, C., Sato, S., Sorokina, I., Parmely, T. J., Conaway, R. C., and Conaway, J. W. (2003) J. Biol. Chem. 278, 42733-42736) [10].
  • Importantly, small interfering RNA knockdown of TRRAP in HeLa cells or TRRAP knockout in mouse embryonic stem cells inhibit the DSB end-joining efficiency and the precise nonhomologous end-joining process, further suggesting a functional involvement of TRRAP in the DSB repair processes [11].
  • To address this issue, we used hepatic cell lines (HepG2) with reduced endogenous TRRAP expression through antisense RNA expression or with overexpressed TRRAP or other major coactivators [12].

Associations of TRRAP with chemical compounds

  • The alanine-replaced BAF53 mutants also stimulated p53-dependent transcription, in which the SWI/SNF and TRRAP complexes are involved [13].
  • Estrogen stimulation enhanced the c-MYC-ERalpha interaction and facilitated the association of ERalpha, c-MYC, and the coactivator TRRAP with these estrogen-responsive promoters, resulting in chromatin remodeling and increased transcription [14].

Physical interactions of TRRAP

  • In vitro analysis demonstrates that p53 directly binds to a TRRAP domain previously shown to be an activator docking site [8].
  • These findings suggest a model in which p53 directly recruits a TRRAP/acetyltransferase complex to the mdm2 gene to activate transcription [8].

Regulatory relationships of TRRAP

  • An hGCN5/TRRAP histone acetyltransferase complex co-activates BRCA1 transactivation function through histone modification [15].
  • Expression of antisense TRRAP RNA in HepG2 cells abolished the ligand-induced expression of LXRalpha target genes [12].

Other interactions of TRRAP

  • Accordingly, wild-type L-Myc is much less efficient in TRRAP binding, activation of the silent TERT gene, and transformation of primary fibroblasts [9].
  • E2F transcriptional activation requires TRRAP and GCN5 cofactors [16].
  • Here we report cloning and characterization of the 400 kDa PCAF-associated factor referred to as PAF400 [7].
  • Furthermore, recruitment of TRRAP is required for c-Myc- or N-Myc-mediated oncogenic transformation but not for the partial restoration of the growth defect in myc-null fibroblasts [9].
  • However, unlike the other members of the ATM superfamily, PAF400 is not a protein kinase as judged from the lack of kinase motif and autophosphorylation activity [7].

Analytical, diagnostic and therapeutic context of TRRAP


  1. Nuclear receptor function requires a TFTC-type histone acetyl transferase complex. Yanagisawa, J., Kitagawa, H., Yanagida, M., Wada, O., Ogawa, S., Nakagomi, M., Oishi, H., Yamamoto, Y., Nagasawa, H., McMahon, S.B., Cole, M.D., Tora, L., Takahashi, N., Kato, S. Mol. Cell (2002) [Pubmed]
  2. The adenovirus E1A oncoprotein recruits the cellular TRRAP/GCN5 histone acetyltransferase complex. Lang, S.E., Hearing, P. Oncogene (2003) [Pubmed]
  3. Functional and mutational analysis of conjugative transfer region 1 (Tra1) from the IncHI1 plasmid R27. Lawley, T.D., Gilmour, M.W., Gunton, J.E., Standeven, L.J., Taylor, D.E. J. Bacteriol. (2002) [Pubmed]
  4. The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins. McMahon, S.B., Van Buskirk, H.A., Dugan, K.A., Copeland, T.D., Cole, M.D. Cell (1998) [Pubmed]
  5. In vivo target of a transcriptional activator revealed by fluorescence resonance energy transfer. Bhaumik, S.R., Raha, T., Aiello, D.P., Green, M.R. Genes Dev. (2004) [Pubmed]
  6. Regulation of cyclin D2 gene expression by the Myc/Max/Mad network: Myc-dependent TRRAP recruitment and histone acetylation at the cyclin D2 promoter. Bouchard, C., Dittrich, O., Kiermaier, A., Dohmann, K., Menkel, A., Eilers, M., Lüscher, B. Genes Dev. (2001) [Pubmed]
  7. The 400 kDa subunit of the PCAF histone acetylase complex belongs to the ATM superfamily. Vassilev, A., Yamauchi, J., Kotani, T., Prives, C., Avantaggiati, M.L., Qin, J., Nakatani, Y. Mol. Cell (1998) [Pubmed]
  8. Transcriptional regulation of the mdm2 oncogene by p53 requires TRRAP acetyltransferase complexes. Ard, P.G., Chatterjee, C., Kunjibettu, S., Adside, L.R., Gralinski, L.E., McMahon, S.B. Mol. Cell. Biol. (2002) [Pubmed]
  9. TRRAP-dependent and TRRAP-independent transcriptional activation by Myc family oncoproteins. Nikiforov, M.A., Chandriani, S., Park, J., Kotenko, I., Matheos, D., Johnsson, A., McMahon, S.B., Cole, M.D. Mol. Cell. Biol. (2002) [Pubmed]
  10. The mammalian YL1 protein is a shared subunit of the TRRAP/TIP60 histone acetyltransferase and SRCAP complexes. Cai, Y., Jin, J., Florens, L., Swanson, S.K., Kusch, T., Li, B., Workman, J.L., Washburn, M.P., Conaway, R.C., Conaway, J.W. J. Biol. Chem. (2005) [Pubmed]
  11. The transcriptional histone acetyltransferase cofactor TRRAP associates with the MRN repair complex and plays a role in DNA double-strand break repair. Robert, F., Hardy, S., Nagy, Z., Baldeyron, C., Murr, R., Déry, U., Masson, J.Y., Papadopoulo, D., Herceg, Z., Tora, L. Mol. Cell. Biol. (2006) [Pubmed]
  12. TRRAP as a hepatic coactivator of LXR and FXR function. Unno, A., Takada, I., Takezawa, S., Oishi, H., Baba, A., Shimizu, T., Tokita, A., Yanagisawa, J., Kato, S. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  13. Effects of Ser2 and Tyr6 mutants of BAF53 on cell growth and p53-dependent transcription. Lee, J.H., Lee, J.Y., Chang, S.H., Kang, M.J., Kwon, H. Mol. Cells (2005) [Pubmed]
  14. Combinatorial analysis of transcription factor partners reveals recruitment of c-MYC to estrogen receptor-alpha responsive promoters. Cheng, A.S., Jin, V.X., Fan, M., Smith, L.T., Liyanarachchi, S., Yan, P.S., Leu, Y.W., Chan, M.W., Plass, C., Nephew, K.P., Davuluri, R.V., Huang, T.H. Mol. Cell (2006) [Pubmed]
  15. An hGCN5/TRRAP histone acetyltransferase complex co-activates BRCA1 transactivation function through histone modification. Oishi, H., Kitagawa, H., Wada, O., Takezawa, S., Tora, L., Kouzu-Fujita, M., Takada, I., Yano, T., Yanagisawa, J., Kato, S. J. Biol. Chem. (2006) [Pubmed]
  16. E2F transcriptional activation requires TRRAP and GCN5 cofactors. Lang, S.E., McMahon, S.B., Cole, M.D., Hearing, P. J. Biol. Chem. (2001) [Pubmed]
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