CRSP3 explained

Mediator of RNA polymerase II transcription subunit 23 is an enzyme that in humans is encoded by the MED23 gene.^{[1] [2]}

Function

The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. This protein also acts as a metastasis suppressor. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene.^[2]

Interactions

CRSP3 has been shown to interact with Estrogen receptor alpha,^[3] CEBPB^[4] and Cyclin-dependent kinase 8.^{[3] [5]}

Further reading

• Rachez C, Lemon BD, Suldan Z, Bromleigh V, Gamble M, Näär AM, Erdjument-Bromage H, Tempst P, Freedman LP . Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex . Nature . 398 . 6730 . 824–8 . Apr 1999 . 10235266 . 10.1038/19783 . 1999Natur.398..824R . 204992765 .
• Näär AM, Beaurang PA, Zhou S, Abraham S, Solomon W, Tjian R . Composite co-activator ARC mediates chromatin-directed transcriptional activation . Nature . 398 . 6730 . 828–32 . Apr 1999 . 10235267 . 10.1038/19789 . 1999Natur.398..828N . 23646963 .
• Boyer TG, Martin ME, Lees E, Ricciardi RP, Berk AJ . Mammalian Srb/Mediator complex is targeted by adenovirus E1A protein . Nature . 399 . 6733 . 276–9 . May 1999 . 10353252 . 10.1038/20466 . 1999Natur.399..276B . 4400507 .
• Nagase T, Ishikawa K, Kikuno R, Hirosawa M, Nomura N, Ohara O . Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 6 . 5 . 337–45 . Oct 1999 . 10574462 . 10.1093/dnares/6.5.337 . free .
• Ko L, Cardona GR, Chin WW . Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator . Proceedings of the National Academy of Sciences of the United States of America . 97 . 11 . 6212–7 . May 2000 . 10823961 . 18584 . 10.1073/pnas.97.11.6212 . 2000PNAS...97.6212K . free .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination . Genome Research . 10 . 11 . 1788–95 . Nov 2000 . 11076863 . 310948 . 10.1101/gr.143000 .
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs . Genome Research . 11 . 3 . 422–35 . Mar 2001 . 11230166 . 311072 . 10.1101/gr.GR1547R .
• Stevens JL, Cantin GT, Wang G, Shevchenko A, Shevchenko A, Berk AJ . Transcription control by E1A and MAP kinase pathway via Sur2 mediator subunit . Science . 296 . 5568 . 755–8 . Apr 2002 . 11934987 . 10.1126/science.1068943 . 2002Sci...296..755S . 19392260 . free .
• Asada S, Choi Y, Yamada M, Wang SC, Hung MC, Qin J, Uesugi M . External control of Her2 expression and cancer cell growth by targeting a Ras-linked coactivator . Proceedings of the National Academy of Sciences of the United States of America . 99 . 20 . 12747–52 . Oct 2002 . 12242338 . 130531 . 10.1073/pnas.202162199 . 2002PNAS...9912747A . free .
• Nakayama M, Kikuno R, Ohara O . Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs . Genome Research . 12 . 11 . 1773–84 . Nov 2002 . 12421765 . 187542 . 10.1101/gr.406902 .
• Goldberg SF, Miele ME, Hatta N, Takata M, Paquette-Straub C, Freedman LP, Welch DR . Melanoma metastasis suppression by chromosome 6: evidence for a pathway regulated by CRSP3 and TXNIP . Cancer Research . 63 . 2 . 432–40 . Jan 2003 . 12543799 .
• Sato S, Tomomori-Sato C, Banks CA, Parmely TJ, Sorokina I, Brower CS, Conaway RC, Conaway JW . A mammalian homolog of Drosophila melanogaster transcriptional coactivator intersex is a subunit of the mammalian Mediator complex . The Journal of Biological Chemistry . 278 . 50 . 49671–4 . Dec 2003 . 14576168 . 10.1074/jbc.C300444200 . free .
• Tomomori-Sato C, Sato S, Parmely TJ, Banks CA, Sorokina I, Florens L, Zybailov B, Washburn MP, Brower CS, Conaway RC, Conaway JW . A mammalian mediator subunit that shares properties with Saccharomyces cerevisiae mediator subunit Cse2 . The Journal of Biological Chemistry . 279 . 7 . 5846–51 . Feb 2004 . 14638676 . 10.1074/jbc.M312523200 . free .
• Mo X, Kowenz-Leutz E, Xu H, Leutz A . Ras induces mediator complex exchange on C/EBP beta . Molecular Cell . 13 . 2 . 241–50 . Jan 2004 . 14759369 . 10.1016/S1097-2765(03)00521-5 . free .
• Sato S, Tomomori-Sato C, Parmely TJ, Florens L, Zybailov B, Swanson SK, Banks CA, Jin J, Cai Y, Washburn MP, Conaway JW, Conaway RC . A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology . Molecular Cell . 14 . 5 . 685–91 . Jun 2004 . 15175163 . 10.1016/j.molcel.2004.05.006 . free .
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A . From ORFeome to biology: a functional genomics pipeline . Genome Research . 14 . 10B . 2136–44 . Oct 2004 . 15489336 . 528930 . 10.1101/gr.2576704 .

Notes and References

1. Ryu S, Zhou S, Ladurner AG, Tjian R . The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1 . Nature . 397 . 6718 . 446–50 . Feb 1999 . 9989412 . 10.1038/17141 . 1999Natur.397..446R . 4405569 . 11858/00-001M-0000-0019-A36A-8 . free .
2. Web site: Entrez Gene: CRSP3 cofactor required for Sp1 transcriptional activation, subunit 3, 130kDa.
3. Kang YK, Guermah M, Yuan CX, Roeder RG . The TRAP/Mediator coactivator complex interacts directly with estrogen receptors alpha and beta through the TRAP220 subunit and directly enhances estrogen receptor function in vitro . Proceedings of the National Academy of Sciences of the United States of America . 99 . 5 . 2642–7 . Mar 2002 . 11867769 . 122401 . 10.1073/pnas.261715899 . 2002PNAS...99.2642K . free .
4. Mo X, Kowenz-Leutz E, Xu H, Leutz A . Ras induces mediator complex exchange on C/EBP beta . Molecular Cell . 13 . 2 . 241–50 . Jan 2004 . 14759369 . 10.1016/S1097-2765(03)00521-5 . free .
5. Wang G, Cantin GT, Stevens JL, Berk AJ . Characterization of mediator complexes from HeLa cell nuclear extract . Molecular and Cellular Biology . 21 . 14 . 4604–13 . Jul 2001 . 11416138 . 87123 . 10.1128/MCB.21.14.4604-4613.2001 .