GPS2 (gene) explained

G protein pathway suppressor 2 is a protein that in humans is encoded by the GPS2 gene.^{[1] [2]}

Function

This gene encodes a protein involved in G protein-mitogen-activated protein kinase (MAPK) signaling cascades. When overexpressed in mammalian cells, this gene could potently suppress a RAS- and MAPK-mediated signal and interfere with JNK activity, suggesting that the function of this gene may be signal repression. The encoded protein is an integral subunit of the NCOR1-HDAC3 (nuclear receptor corepressor 1-histone deacetylase 3) complex, and it was shown that the complex inhibits JNK activation through this subunit and thus could potentially provide an alternative mechanism for hormone-mediated antagonism of AP1 (activator protein 1) function.^[2]

Interactions

GPS2 (gene) has been shown to interact with:

• C21orf7,^[3]
• Cyclin A1,^[4]
• EP300,^[5]
• HDAC3,
• NCOR1,^{[6] [7]}
• P53,^[8] and
• TBL1X.^[9]

Further reading

• Jin DY, Teramoto H, Giam CZ, Chun RF, Gutkind JS, Jeang KT . A human suppressor of c-Jun N-terminal kinase 1 activation by tumor necrosis factor alpha . The Journal of Biological Chemistry . 272 . 41 . 25816–23 . Oct 1997 . 9325311 . 10.1074/jbc.272.41.25816 . free .
• Peng YC, Breiding DE, Sverdrup F, Richard J, Androphy EJ . AMF-1/Gps2 binds p300 and enhances its interaction with papillomavirus E2 proteins . Journal of Virology . 74 . 13 . 5872–9 . Jul 2000 . 10846067 . 112082 . 10.1128/JVI.74.13.5872-5879.2000 .
• Degenhardt YY, Silverstein SJ . Gps2, a protein partner for human papillomavirus E6 proteins . Journal of Virology . 75 . 1 . 151–60 . Jan 2001 . 11119584 . 113908 . 10.1128/JVI.75.1.151-160.2001 .
• 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 .
• Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O . Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 8 . 2 . 85–95 . Apr 2001 . 11347906 . 10.1093/dnares/8.2.85 . free .
• Peng YC, Kuo F, Breiding DE, Wang YF, Mansur CP, Androphy EJ . AMF1 (GPS2) modulates p53 transactivation . Molecular and Cellular Biology . 21 . 17 . 5913–24 . Sep 2001 . 11486030 . 87310 . 10.1128/MCB.21.17.5913-5924.2001 .
• Zhang J, Kalkum M, Chait BT, Roeder RG . The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2 . Molecular Cell . 9 . 3 . 611–23 . Mar 2002 . 11931768 . 10.1016/S1097-2765(02)00468-9 . free .
• Yoon HG, Chan DW, Huang ZQ, Li J, Fondell JD, Qin J, Wong J . Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1 . The EMBO Journal . 22 . 6 . 1336–46 . Mar 2003 . 12628926 . 151047 . 10.1093/emboj/cdg120 .
• Yoon HG, Chan DW, Reynolds AB, Qin J, Wong J . N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso . Molecular Cell . 12 . 3 . 723–34 . Sep 2003 . 14527417 . 10.1016/j.molcel.2003.08.008 . free .
• Diederichs S, Bäumer N, Ji P, Metzelder SK, Idos GE, Cauvet T, Wang W, Möller M, Pierschalski S, Gromoll J, Schrader MG, Koeffler HP, Berdel WE, Serve H, Müller-Tidow C . Identification of interaction partners and substrates of the cyclin A1-CDK2 complex . The Journal of Biological Chemistry . 279 . 32 . 33727–41 . Aug 2004 . 15159402 . 10.1074/jbc.M401708200 . free .
• Lee TH, Yi W, Griswold MD, Zhu F, Her C . Formation of hMSH4-hMSH5 heterocomplex is a prerequisite for subsequent GPS2 recruitment . DNA Repair . 5 . 1 . 32–42 . Jan 2006 . 16122992 . 10.1016/j.dnarep.2005.07.004 .
• Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE . A human protein-protein interaction network: a resource for annotating the proteome . Cell . 122 . 6 . 957–68 . Sep 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . 11858/00-001M-0000-0010-8592-0 . 8235923 . free .
• Sanyal S, Båvner A, Haroniti A, Nilsson LM, Lundåsen T, Rehnmark S, Witt MR, Einarsson C, Talianidis I, Gustafsson JA, Treuter E . Involvement of corepressor complex subunit GPS2 in transcriptional pathways governing human bile acid biosynthesis . Proceedings of the National Academy of Sciences of the United States of America . 104 . 40 . 15665–70 . Oct 2007 . 17895379 . 2000397 . 10.1073/pnas.0706736104 . 2007PNAS..10415665S . free .

Notes and References

1. Spain BH, Bowdish KS, Pacal AR, Staub SF, Koo D, Chang CY, Xie W, Colicelli J . Two human cDNAs, including a homolog of Arabidopsis FUS6 (COP11), suppress G-protein- and mitogen-activated protein kinase-mediated signal transduction in yeast and mammalian cells . Molecular and Cellular Biology . 16 . 12 . 6698–706 . Dec 1996 . 8943324 . 231672 . 10.1128/mcb.16.12.6698.
2. Web site: Entrez Gene: GPS2 G protein pathway suppressor 2.
3. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . Oct 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
4. Diederichs S, Bäumer N, Ji P, Metzelder SK, Idos GE, Cauvet T, Wang W, Möller M, Pierschalski S, Gromoll J, Schrader MG, Koeffler HP, Berdel WE, Serve H, Müller-Tidow C . Identification of interaction partners and substrates of the cyclin A1-CDK2 complex . The Journal of Biological Chemistry . 279 . 32 . 33727–41 . Aug 2004 . 15159402 . 10.1074/jbc.M401708200 . free .
5. Peng YC, Breiding DE, Sverdrup F, Richard J, Androphy EJ . AMF-1/Gps2 binds p300 and enhances its interaction with papillomavirus E2 proteins . Journal of Virology . 74 . 13 . 5872–9 . Jul 2000 . 10846067 . 112082 . 10.1128/jvi.74.13.5872-5879.2000.
6. Yoon HG, Chan DW, Reynolds AB, Qin J, Wong J . N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso . Molecular Cell . 12 . 3 . 723–34 . Sep 2003 . 14527417 . 10.1016/j.molcel.2003.08.008. free .
7. Yoon HG, Chan DW, Huang ZQ, Li J, Fondell JD, Qin J, Wong J . Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1 . The EMBO Journal . 22 . 6 . 1336–46 . Mar 2003 . 12628926 . 151047 . 10.1093/emboj/cdg120 .
8. Peng YC, Kuo F, Breiding DE, Wang YF, Mansur CP, Androphy EJ . AMF1 (GPS2) modulates p53 transactivation . Molecular and Cellular Biology . 21 . 17 . 5913–24 . Sep 2001 . 11486030 . 87310 . 10.1128/mcb.21.17.5913-5924.2001.
9. Zhang J, Kalkum M, Chait BT, Roeder RG . The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2 . Molecular Cell . 9 . 3 . 611–23 . Mar 2002 . 11931768 . 10.1016/s1097-2765(02)00468-9. free .