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Protein-coding gene in the species Homo sapiens
Transformation/transcription domain-associated protein , also known as TRRAP , is a protein that in humans is encoded by the TRRAP gene .[ 5] [ 6] phosphatidylinositol 3-kinase-related kinase protein family.
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.[ 7]
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.[ 8] [ 9]
Transformation/transcription domain-associated protein has been shown to interact with:
^ a b c GRCh38: Ensembl release 89: ENSG00000196367 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000045482 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ a b c McMahon SB, Van Buskirk HA, Dugan KA, Copeland TD, Cole MD (August 1998). "The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins" . Cell . 94 (3): 363–74. doi :10.1016/S0092-8674(00)81479-8 PMID 9708738 . S2CID 17693834 . ^ Vassilev A, Yamauchi J, Kotani T, Prives C, Avantaggiati ML, Qin J, Nakatani Y (December 1998). "The 400 kDa subunit of the PCAF histone acetylase complex belongs to the ATM superfamily" . Mol. Cell . 2 (6): 869–75. doi :10.1016/S1097-2765(00)80301-9 PMID 9885574 . ^ Murr R, Vaissière T, Sawan C, Shukla V, Herceg Z (August 2007). "Orchestration of chromatin-based processes: mind the TRRAP". Oncogene . 26 (37): 5358–72. doi :10.1038/sj.onc.1210605 . PMID 17694078 . S2CID 22598445 . ^ Robert F, Hardy S, Nagy Z, Baldeyron C, Murr R, Déry U, Masson JY, Papadopoulo D, Herceg Z, Tora L (January 2006). "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. doi :10.1128/MCB.26.2.402-412.2006 . PMC 1346889 PMID 16382133 . ^ Herceg Z, Wang ZQ (March 2005). "Rendez-vous at mitosis: TRRAPed in the chromatin" . Cell Cycle . 4 (3): 383–7. doi :10.4161/cc.4.3.1546 PMID 15711126 . ^ a b Park J, Wood MA, Cole MD (March 2002). "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. doi :10.1128/mcb.22.5.1307-1316.2002 . PMC 134713 PMID 11839798 . ^ a b Fuchs M, Gerber J, Drapkin R, Sif S, Ikura T, Ogryzko V, Lane WS, Nakatani Y, Livingston DM (August 2001). "The p400 complex is an essential E1A transformation target" . Cell . 106 (3): 297–307. doi :10.1016/s0092-8674(01)00450-0 PMID 11509179 . S2CID 15634637 . ^ a b McMahon SB, Wood MA, Cole MD (January 2000). "The essential cofactor TRRAP recruits the histone acetyltransferase hGCN5 to c-Myc" . Mol. Cell. Biol . 20 (2): 556–62. doi :10.1128/mcb.20.2.556-562.2000 . PMC 85131 PMID 10611234 . ^ a b Liu X, Tesfai J, Evrard YA, Dent SY, Martinez E (May 2003). "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. doi :10.1074/jbc.M211795200 PMC 4031917 PMID 12660246 . ^ a b Martinez E, Palhan VB, Tjernberg A, Lymar ES, Gamper AM, Kundu TK, Chait BT, Roeder RG (October 2001). "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. doi :10.1128/MCB.21.20.6782-6795.2001 . PMC 99856 PMID 11564863 .
Herceg Z, Wang ZQ (2006). "Rendez-vous at mitosis: TRRAPed in the chromatin" . Cell Cycle . 4 (3): 383–7. doi :10.4161/cc.4.3.1546 PMID 15711126 . Murr R, Vaissière T, Sawan C, Shukla V, Herceg Z (2007). "Orchestration of chromatin-based processes: mind the TRRAP". Oncogene . 26 (37): 5358–72. doi :10.1038/sj.onc.1210605 . PMID 17694078 . S2CID 22598445 . McMahon SB, Van Buskirk HA, Dugan KA, Copeland TD, Cole MD (1998). "The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins" . Cell . 94 (3): 363–74. doi :10.1016/S0092-8674(00)81479-8 PMID 9708738 . S2CID 17693834 . Vassilev A, Yamauchi J, Kotani T, Prives C, Avantaggiati ML, Qin J, Nakatani Y (1999). "The 400 kDa subunit of the PCAF histone acetylase complex belongs to the ATM superfamily" . Mol. Cell . 2 (6): 869–75. doi :10.1016/S1097-2765(00)80301-9 PMID 9885574 . Brand M, Yamamoto K, Staub A, Tora L (1999). "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. doi :10.1074/jbc.274.26.18285 PMID 10373431 . McMahon SB, Wood MA, Cole MD (2000). "The Essential Cofactor TRRAP Recruits the Histone Acetyltransferase hGCN5 to c-Myc" . Mol. Cell. Biol . 20 (2): 556–62. doi :10.1128/MCB.20.2.556-562.2000 . PMC 85131 PMID 10611234 . Ikura T, Ogryzko VV, Grigoriev M, Groisman R, Wang J, Horikoshi M, Scully R, Qin J, Nakatani Y (2000). "Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis" . Cell . 102 (4): 463–73. doi :10.1016/S0092-8674(00)00051-9 PMID 10966108 . S2CID 18047169 . Brand M, Moggs JG, Oulad-Abdelghani M, Lejeune F, Dilworth FJ, Stevenin J, Almouzni G, Tora L (2001). "UV-damaged DNA-binding protein in the TFTC complex links DNA damage recognition to nucleosome acetylation" . EMBO J . 20 (12): 3187–96. doi :10.1093/emboj/20.12.3187 . PMC 150203 PMID 11406595 . Lee YJ, Chung TS, Yoon YS, Lee MS, Han SH, Seong GJ, Ahn KJ (2001). "The role of functional MR imaging in patients with ischemia in the visual cortex" . American Journal of Neuroradiology . 22 (6): 1043–9. PMC 7974786 PMID 11415895 . Lang SE, McMahon SB, Cole MD, Hearing P (2001). "E2F transcriptional activation requires TRRAP and GCN5 cofactors" . J. Biol. Chem . 276 (35): 32627–34. doi :10.1074/jbc.M102067200 PMID 11418595 . Park J, Kunjibettu S, McMahon SB, Cole MD (2001). "The ATM-related domain of TRRAP is required for histone acetyltransferase recruitment and Myc-dependent oncogenesis" . Genes Dev . 15 (13): 1619–24. doi :10.1101/gad.900101 . PMC 312730 PMID 11445536 . Fuchs M, Gerber J, Drapkin R, Sif S, Ikura T, Ogryzko V, Lane WS, Nakatani Y, Livingston DM (2001). "The p400 complex is an essential E1A transformation target" . Cell . 106 (3): 297–307. doi :10.1016/S0092-8674(01)00450-0 PMID 11509179 . S2CID 15634637 . Martinez E, Palhan VB, Tjernberg A, Lymar ES, Gamper AM, Kundu TK, Chait BT, Roeder RG (2001). "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. doi :10.1128/MCB.21.20.6782-6795.2001 . PMC 99856 PMID 11564863 . Park J, Wood MA, Cole MD (2002). "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. doi :10.1128/MCB.22.5.1307-1316.2002 . PMC 134713 PMID 11839798 . Nikiforov MA, Chandriani S, Park J, Kotenko I, Matheos D, Johnsson A, McMahon SB, Cole MD (2002). "TRRAP-Dependent and TRRAP-Independent Transcriptional Activation by Myc Family Oncoproteins" . Mol. Cell. Biol . 22 (14): 5054–63. doi :10.1128/MCB.22.14.5054-5063.2002 . PMC 139788 PMID 12077335 . Ard PG, Chatterjee C, Kunjibettu S, Adside LR, Gralinski LE, McMahon SB (2002). "Transcriptional Regulation of the mdm2 Oncogene by p53 Requires TRRAP Acetyltransferase Complexes" . Mol. Cell. Biol . 22 (16): 5650–61. doi :10.1128/MCB.22.16.5650-5661.2002 . PMC 133988 PMID 12138177 . Cavusoglu N, Brand M, Tora L, Van Dorsselaer A (2003). "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. doi :10.1002/pmic.200390030 . PMID 12601814 . S2CID 6035986 . Liu X, Tesfai J, Evrard YA, Dent SY, Martinez E (2003). "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. doi :10.1074/jbc.M211795200 PMC 4031917 PMID 12660246 .
