1wxp

Structural highlights

Function

THOC1_HUMAN Component of the THO subcomplex of the TREX complex. The TREX complex specifically associates with spliced mRNA and not with unspliced pre-mRNA. It is recruited to spliced mRNAs by a transcription-independent mechanism. Binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export. The recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1. DDX39B functions as a bridge between ALYREF/THOC4 and the THO complex. The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production. The recruitment of the TREX complex to the intronless viral mRNA occurs via an interaction between KSHV ORF57 protein and ALYREF/THOC4.^{[1] [2] [3] [4] [5] [6] [7] [8] [9]} Regulates transcriptional elongation of a subset of genes. Participates in an apoptotic pathway which is characterized by activation of caspase-6, increases in the expression of BAK1 and BCL2L1 and activation of NF-kappa-B. This pathway does not require p53/TP53, nor does the presence of p53/TP53 affect the efficiency of cell killing. Activates a G2/M cell cycle checkpoint prior to the onset of apoptosis. Apoptosis is inhibited by association with RB1.^{[10] [11] [12] [13] [14] [15] [16] [17] [18]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Doostzadeh-Cizeron J, Evans R, Yin S, Goodrich DW. Apoptosis induced by the nuclear death domain protein p84N5 is inhibited by association with Rb protein. Mol Biol Cell. 1999 Oct;10(10):3251-61. PMID:10512864
2. ↑ Doostzadeh-Cizeron J, Yin S, Goodrich DW. Apoptosis induced by the nuclear death domain protein p84N5 is associated with caspase-6 and NF-kappa B activation. J Biol Chem. 2000 Aug 18;275(33):25336-41. PMID:10840029 doi:http://dx.doi.org/10.1074/jbc.M000793200
3. ↑ Doostzadeh-Cizeron J, Terry NH, Goodrich DW. The nuclear death domain protein p84N5 activates a G2/M cell cycle checkpoint prior to the onset of apoptosis. J Biol Chem. 2001 Jan 12;276(2):1127-32. PMID:11050087 doi:http://dx.doi.org/10.1074/jbc.M006944200
4. ↑ Strasser K, Masuda S, Mason P, Pfannstiel J, Oppizzi M, Rodriguez-Navarro S, Rondon AG, Aguilera A, Struhl K, Reed R, Hurt E. TREX is a conserved complex coupling transcription with messenger RNA export. Nature. 2002 May 16;417(6886):304-8. Epub 2002 Apr 28. PMID:11979277 doi:http://dx.doi.org/10.1038/nature746
5. ↑ Guo S, Hakimi MA, Baillat D, Chen X, Farber MJ, Klein-Szanto AJ, Cooch NS, Godwin AK, Shiekhattar R. Linking transcriptional elongation and messenger RNA export to metastatic breast cancers. Cancer Res. 2005 Apr 15;65(8):3011-6. PMID:15833825 doi:http://dx.doi.org/10.1158/0008-5472.CAN-04-3624
6. ↑ Masuda S, Das R, Cheng H, Hurt E, Dorman N, Reed R. Recruitment of the human TREX complex to mRNA during splicing. Genes Dev. 2005 Jul 1;19(13):1512-7. PMID:15998806 doi:http://dx.doi.org/10.1101/gad.1302205
7. ↑ Li Y, Wang X, Zhang X, Goodrich DW. Human hHpr1/p84/Thoc1 regulates transcriptional elongation and physically links RNA polymerase II and RNA processing factors. Mol Cell Biol. 2005 May;25(10):4023-33. PMID:15870275 doi:http://dx.doi.org/10.1128/MCB.25.10.4023-4033.2005
8. ↑ Cheng H, Dufu K, Lee CS, Hsu JL, Dias A, Reed R. Human mRNA export machinery recruited to the 5' end of mRNA. Cell. 2006 Dec 29;127(7):1389-400. PMID:17190602 doi:http://dx.doi.org/10.1016/j.cell.2006.10.044
9. ↑ Boyne JR, Colgan KJ, Whitehouse A. Recruitment of the complete hTREX complex is required for Kaposi's sarcoma-associated herpesvirus intronless mRNA nuclear export and virus replication. PLoS Pathog. 2008 Oct;4(10):e1000194. doi: 10.1371/journal.ppat.1000194. Epub, 2008 Oct 31. PMID:18974867 doi:http://dx.doi.org/10.1371/journal.ppat.1000194
10. ↑ Doostzadeh-Cizeron J, Evans R, Yin S, Goodrich DW. Apoptosis induced by the nuclear death domain protein p84N5 is inhibited by association with Rb protein. Mol Biol Cell. 1999 Oct;10(10):3251-61. PMID:10512864
11. ↑ Doostzadeh-Cizeron J, Yin S, Goodrich DW. Apoptosis induced by the nuclear death domain protein p84N5 is associated with caspase-6 and NF-kappa B activation. J Biol Chem. 2000 Aug 18;275(33):25336-41. PMID:10840029 doi:http://dx.doi.org/10.1074/jbc.M000793200
12. ↑ Doostzadeh-Cizeron J, Terry NH, Goodrich DW. The nuclear death domain protein p84N5 activates a G2/M cell cycle checkpoint prior to the onset of apoptosis. J Biol Chem. 2001 Jan 12;276(2):1127-32. PMID:11050087 doi:http://dx.doi.org/10.1074/jbc.M006944200
13. ↑ Strasser K, Masuda S, Mason P, Pfannstiel J, Oppizzi M, Rodriguez-Navarro S, Rondon AG, Aguilera A, Struhl K, Reed R, Hurt E. TREX is a conserved complex coupling transcription with messenger RNA export. Nature. 2002 May 16;417(6886):304-8. Epub 2002 Apr 28. PMID:11979277 doi:http://dx.doi.org/10.1038/nature746
14. ↑ Guo S, Hakimi MA, Baillat D, Chen X, Farber MJ, Klein-Szanto AJ, Cooch NS, Godwin AK, Shiekhattar R. Linking transcriptional elongation and messenger RNA export to metastatic breast cancers. Cancer Res. 2005 Apr 15;65(8):3011-6. PMID:15833825 doi:http://dx.doi.org/10.1158/0008-5472.CAN-04-3624
15. ↑ Masuda S, Das R, Cheng H, Hurt E, Dorman N, Reed R. Recruitment of the human TREX complex to mRNA during splicing. Genes Dev. 2005 Jul 1;19(13):1512-7. PMID:15998806 doi:http://dx.doi.org/10.1101/gad.1302205
16. ↑ Li Y, Wang X, Zhang X, Goodrich DW. Human hHpr1/p84/Thoc1 regulates transcriptional elongation and physically links RNA polymerase II and RNA processing factors. Mol Cell Biol. 2005 May;25(10):4023-33. PMID:15870275 doi:http://dx.doi.org/10.1128/MCB.25.10.4023-4033.2005
17. ↑ Cheng H, Dufu K, Lee CS, Hsu JL, Dias A, Reed R. Human mRNA export machinery recruited to the 5' end of mRNA. Cell. 2006 Dec 29;127(7):1389-400. PMID:17190602 doi:http://dx.doi.org/10.1016/j.cell.2006.10.044
18. ↑ Boyne JR, Colgan KJ, Whitehouse A. Recruitment of the complete hTREX complex is required for Kaposi's sarcoma-associated herpesvirus intronless mRNA nuclear export and virus replication. PLoS Pathog. 2008 Oct;4(10):e1000194. doi: 10.1371/journal.ppat.1000194. Epub, 2008 Oct 31. PMID:18974867 doi:http://dx.doi.org/10.1371/journal.ppat.1000194