Transformation/transcription domain-associated protein explained

Transformation/transcription domain-associated protein, also known as TRRAP, is a protein that in humans is encoded by the TRRAP gene.^{[1] [2]} TRRAP belongs to the phosphatidylinositol 3-kinase-related kinase protein family.

Function

TRRAP is an adaptor 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.^[3]

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.^{[4] [5]}

Interactions

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

• ACTL6A,^[6]
• EP400,
• MAX,^[1]
• Myc,^{[6] [7]}
• PCAF,^{[8] [9]}
• SUPT3H, and
• TAF9.^[10] and

Further reading

• Herceg Z, Wang ZQ . Rendez-vous at mitosis: TRRAPed in the chromatin . Cell Cycle . 4 . 3 . 383–7 . 2006 . 15711126 . 10.4161/cc.4.3.1546 . free .
• Murr R, Vaissière T, Sawan C, Shukla V, Herceg Z . Orchestration of chromatin-based processes: mind the TRRAP . Oncogene . 26 . 37 . 5358–72 . 2007 . 17694078 . 10.1038/sj.onc.1210605 . 22598445 .
• McMahon SB, Van Buskirk HA, Dugan KA, Copeland TD, Cole MD . The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins . Cell . 94 . 3 . 363–74 . 1998 . 9708738 . 10.1016/S0092-8674(00)81479-8 . 17693834 . free .
• Vassilev A, Yamauchi J, Kotani T, Prives C, Avantaggiati ML, Qin J, Nakatani Y . The 400 kDa subunit of the PCAF histone acetylase complex belongs to the ATM superfamily . Mol. Cell . 2 . 6 . 869–75 . 1999 . 9885574 . 10.1016/S1097-2765(00)80301-9 . free .
• Brand M, Yamamoto K, Staub A, Tora L . Identification of TATA-binding protein-free TAFII-containing complex subunits suggests a role in nucleosome acetylation and signal transduction . J. Biol. Chem. . 274 . 26 . 18285–9 . 1999 . 10373431 . 10.1074/jbc.274.26.18285 . free .
• McMahon SB, Wood MA, Cole MD . The Essential Cofactor TRRAP Recruits the Histone Acetyltransferase hGCN5 to c-Myc . Mol. Cell. Biol. . 20 . 2 . 556–62 . 2000 . 10611234 . 85131 . 10.1128/MCB.20.2.556-562.2000 .
• Ikura T, Ogryzko VV, Grigoriev M, Groisman R, Wang J, Horikoshi M, Scully R, Qin J, Nakatani Y . Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis . Cell . 102 . 4 . 463–73 . 2000 . 10966108 . 10.1016/S0092-8674(00)00051-9 . 18047169 . free .
• Brand M, Moggs JG, Oulad-Abdelghani M, Lejeune F, Dilworth FJ, Stevenin J, Almouzni G, Tora L . UV-damaged DNA-binding protein in the TFTC complex links DNA damage recognition to nucleosome acetylation . EMBO J. . 20 . 12 . 3187–96 . 2001 . 11406595 . 150203 . 10.1093/emboj/20.12.3187 .
• Lee YJ, Chung TS, Yoon YS, Lee MS, Han SH, Seong GJ, Ahn KJ . The role of functional MR imaging in patients with ischemia in the visual cortex . American Journal of Neuroradiology . 22 . 6 . 1043–9 . 2001 . 11415895 . 7974786 .
• Lang SE, McMahon SB, Cole MD, Hearing P . E2F transcriptional activation requires TRRAP and GCN5 cofactors . J. Biol. Chem. . 276 . 35 . 32627–34 . 2001 . 11418595 . 10.1074/jbc.M102067200 . free .
• Park J, Kunjibettu S, McMahon SB, Cole MD . The ATM-related domain of TRRAP is required for histone acetyltransferase recruitment and Myc-dependent oncogenesis . Genes Dev. . 15 . 13 . 1619–24 . 2001 . 11445536 . 312730 . 10.1101/gad.900101 .
• Fuchs M, Gerber J, Drapkin R, Sif S, Ikura T, Ogryzko V, Lane WS, Nakatani Y, Livingston DM . The p400 complex is an essential E1A transformation target . Cell . 106 . 3 . 297–307 . 2001 . 11509179 . 10.1016/S0092-8674(01)00450-0 . 15634637 . free .
• Martinez E, Palhan VB, Tjernberg A, Lymar ES, Gamper AM, Kundu TK, Chait BT, Roeder RG . Human STAGA Complex Is a Chromatin-Acetylating Transcription Coactivator That Interacts with Pre-mRNA Splicing and DNA Damage-Binding Factors In Vivo . Mol. Cell. Biol. . 21 . 20 . 6782–95 . 2001 . 11564863 . 99856 . 10.1128/MCB.21.20.6782-6795.2001 .
• Park J, Wood MA, Cole MD . BAF53 Forms Distinct Nuclear Complexes and Functions as a Critical c-Myc-Interacting Nuclear Cofactor for Oncogenic Transformation . Mol. Cell. Biol. . 22 . 5 . 1307–16 . 2002 . 11839798 . 134713 . 10.1128/MCB.22.5.1307-1316.2002 .
• Nikiforov MA, Chandriani S, Park J, Kotenko I, Matheos D, Johnsson A, McMahon SB, Cole MD . TRRAP-Dependent and TRRAP-Independent Transcriptional Activation by Myc Family Oncoproteins . Mol. Cell. Biol. . 22 . 14 . 5054–63 . 2002 . 12077335 . 139788 . 10.1128/MCB.22.14.5054-5063.2002 .
• Ard PG, Chatterjee C, Kunjibettu S, Adside LR, Gralinski LE, McMahon SB . Transcriptional Regulation of the mdm2 Oncogene by p53 Requires TRRAP Acetyltransferase Complexes . Mol. Cell. Biol. . 22 . 16 . 5650–61 . 2002 . 12138177 . 133988 . 10.1128/MCB.22.16.5650-5661.2002 .
• Cavusoglu N, Brand M, Tora L, Van Dorsselaer A . Novel subunits of the TATA binding protein free TAFII-containing transcription complex identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry following one-dimensional gel electrophoresis . Proteomics . 3 . 2 . 217–23 . 2003 . 12601814 . 10.1002/pmic.200390030 . 6035986 .
• Liu X, Tesfai J, Evrard YA, Dent SY, Martinez E . c-Myc transformation domain recruits the human STAGA complex and requires TRRAP and GCN5 acetylase activity for transcription activation . J. Biol. Chem. . 278 . 22 . 20405–12 . 2003 . 12660246 . 10.1074/jbc.M211795200 . 4031917. free .

Notes and References

1. McMahon SB, Van Buskirk HA, Dugan KA, Copeland TD, Cole MD . The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins . Cell . 94 . 3 . 363–74 . August 1998 . 9708738 . 10.1016/S0092-8674(00)81479-8 . 17693834 . free .
2. Vassilev A, Yamauchi J, Kotani T, Prives C, Avantaggiati ML, Qin J, Nakatani Y . The 400 kDa subunit of the PCAF histone acetylase complex belongs to the ATM superfamily . Mol. Cell . 2 . 6 . 869–75 . December 1998 . 9885574 . 10.1016/S1097-2765(00)80301-9 . free .
3. Murr R, Vaissière T, Sawan C, Shukla V, Herceg Z . Orchestration of chromatin-based processes: mind the TRRAP . Oncogene . 26 . 37 . 5358–72 . August 2007 . 17694078 . 10.1038/sj.onc.1210605 . 22598445 .
4. Robert F, Hardy S, Nagy Z, Baldeyron C, Murr R, Déry U, Masson JY, Papadopoulo D, Herceg Z, Tora L . 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. . 26 . 2 . 402–12 . January 2006 . 16382133 . 1346889 . 10.1128/MCB.26.2.402-412.2006 .
5. Herceg Z, Wang ZQ . Rendez-vous at mitosis: TRRAPed in the chromatin . Cell Cycle . 4 . 3 . 383–7 . March 2005 . 15711126 . 10.4161/cc.4.3.1546 . free .
6. Park J, Wood MA, Cole MD . BAF53 forms distinct nuclear complexes and functions as a critical c-Myc-interacting nuclear cofactor for oncogenic transformation . Mol. Cell. Biol. . 22 . 5 . 1307–16 . March 2002 . 11839798 . 134713 . 10.1128/mcb.22.5.1307-1316.2002.
7. McMahon SB, Wood MA, Cole MD . The essential cofactor TRRAP recruits the histone acetyltransferase hGCN5 to c-Myc . Mol. Cell. Biol. . 20 . 2 . 556–62 . January 2000 . 10611234 . 85131 . 10.1128/mcb.20.2.556-562.2000.
8. Fuchs M, Gerber J, Drapkin R, Sif S, Ikura T, Ogryzko V, Lane WS, Nakatani Y, Livingston DM . The p400 complex is an essential E1A transformation target . Cell . 106 . 3 . 297–307 . August 2001 . 11509179 . 10.1016/s0092-8674(01)00450-0. 15634637 . free .
9. Liu X, Tesfai J, Evrard YA, Dent SY, Martinez E . c-Myc transformation domain recruits the human STAGA complex and requires TRRAP and GCN5 acetylase activity for transcription activation . J. Biol. Chem. . 278 . 22 . 20405–12 . May 2003 . 12660246 . 4031917 . 10.1074/jbc.M211795200 . free .
10. Martinez E, Palhan VB, Tjernberg A, Lymar ES, Gamper AM, Kundu TK, Chait BT, Roeder RG . Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo . Mol. Cell. Biol. . 21 . 20 . 6782–95 . October 2001 . 11564863 . 99856 . 10.1128/MCB.21.20.6782-6795.2001 .