Transformation/transcription domain-associated protein

Transformation/transcription domain-associated protein
Identifiers
Symbols TRRAP; FLJ10671; PAF350/400; PAF400; STAF40; TR-AP; Tra1
External IDs OMIM: 603015 MGI: 2153272 HomoloGene: 39246 GeneCards: TRRAP Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 8295 100683
Ensembl ENSG00000196367 ENSMUSG00000045482
UniProt Q9Y4A5 Q3TIP5
RefSeq (mRNA) NM_003496 NM_001081362.1
RefSeq (protein) NP_003487 NP_001074831.1
Location (UCSC) Chr 7:
98.48 – 98.61 Mb		 Chr 5:
145.53 – 145.62 Mb
PubMed search [1] [2]

Transformation/transcription domain-associated protein, also known asTRRAP, 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.

Contents

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 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] PCAF,[7][8] Myc,[1][6][7][9] TAF9,[10] Transcription initiation protein SPT3 homolog,[10] MAX[1][9] and EP400.[8]

References

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1346889. 
  5. ^ 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. http://www.landesbioscience.com/journals/cc/article/1546/. 
  6. ^ a b Park, Jeonghyeon; Wood Marcelo A, Cole Michael D (March 2002). "BAF53 Forms Distinct Nuclear Complexes and Functions as a Critical c-Myc-Interacting Nuclear Cofactor for Oncogenic Transformation". Mol. Cell. Biol. (United States) 22 (5): 1307–16. doi:10.1128/MCB.22.5.1307-1316.2002. ISSN 0270-7306. PMC 134713. PMID 11839798. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=134713. 
  7. ^ a b Liu, Xiaohui; Tesfai Jerusalem, Evrard Yvonne A, Dent Sharon Y R, Martinez Ernest (May 2003). "c-Myc transformation domain recruits the human STAGA complex and requires TRRAP and GCN5 acetylase activity for transcription activation". J. Biol. Chem. (United States) 278 (22): 20405–12. doi:10.1074/jbc.M211795200. ISSN 0021-9258. PMID 12660246. 
  8. ^ a b Fuchs, M; Gerber J, Drapkin R, Sif S, Ikura T, Ogryzko V, Lane W S, Nakatani Y, Livingston D M (August 2001). "The p400 complex is an essential E1A transformation target". Cell (United States) 106 (3): 297–307. doi:10.1016/S0092-8674(01)00450-0. ISSN 0092-8674. PMID 11509179. 
  9. ^ a b McMahon, S B; Wood M A, Cole M D (January 2000). "The Essential Cofactor TRRAP Recruits the Histone Acetyltransferase hGCN5 to c-Myc". Mol. Cell. Biol. (UNITED STATES) 20 (2): 556–62. doi:10.1128/MCB.20.2.556-562.2000. ISSN 0270-7306. PMC 85131. PMID 10611234. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85131. 
  10. ^ a b Martinez, E; Palhan V B, Tjernberg A, Lymar E S, Gamper A M, Kundu T K, Chait B T, Roeder R G (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. (United States) 21 (20): 6782–95. doi:10.1128/MCB.21.20.6782-6795.2001. ISSN 0270-7306. PMC 99856. PMID 11564863. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=99856. 

Further reading