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Cited2 modulates TGF-β-mediated upregulation of MMP9

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Abstract

Cited (CBP/p300-interacting transactivators with glutamic acid (E)/aspartic acid (D)-rich C-terminal domain) 2, which is a CBP/p300-binding transcription co-activator without typical DNA-binding domains, has been implicated in control of cell growth and malignant transformation in Rat1 cells. In this report, we provide evidence that Cited2 is an important regulator of transforming growth factor (TGF)-β signaling. Overexpression of Cited2 enhanced TGF-β-mediated transcription of a Smad-Binding Element-containing luciferase reporter construct, SBE4-Luc. This may occur through a direct physical association of Cited2 with Smads 2 and 3, as supported by co-immunoprecipitation, mammalian two-hybrid and glutathione S-transferase-pull down assays. The transcription factor p300, which binds to Smad3, was shown to further enhance the interaction between Cited2 and Smad3, and the transcriptional responses of Smad3 by Cited2 in reporter assays. Cited2 enhances TGF-β-mediated upregulation of matrix metalloproteinase 9 (MMP9) in Cited2 inducible mouse embryo fibroblasts. Overexpression of Cited2 enhanced TGF-β-mediated MMP9 promoter reporter activity. Moreover, knockdown of Cited2 in MDA-MB-231 cells attenuated TGF-β-mediated upregulation of MMP9 and TGF-β-mediated cell invasion. Chromatin immunoprecipitation showed that Cited2 and Smad3 were recruited to MMP9 promoter upon TGF-β stimulation. This is the first demonstration that Cited2 functions as a Smad3/p300-interacting transcriptional co-activator in modulating the expression of MMP9, which could affect tumor cell invasion mediated by TGF-β.

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References

  • Andrews JE, O'Neill MJ, Binder M, Shioda T, Sinclair AH . (2000). Mech Dev 95: 305–308.

  • Attisano L, Wrana JL . (2000). Curr Opin Cell Biol 12: 235–243.

  • Bamforth SD, Braganca J, Eloranta JJ, Murdoch JN, Marques FI, Kranc KR et al. (2001). Nat Genet 29: 469–474.

  • Bandyopadhyay A, Zhu Y, Cibull ML, Bao L, Chen C, Sun L . (1999). Cancer Res 59: 5041–5046.

  • Bannikov GA, Karelina TV, Collier IE, Marmer BL, Goldberg GI . (2002). J Biol Chem 277: 16022–16027.

  • Barbera JP, Rodriguez TA, Greene ND, Weninger WJ, Simeone A, Copp AJ et al. (2002). Hum Mol Genet 11: 283–293.

  • Bhattacharya S, Michels CL, Leung MK, Arany ZP, Kung AL, Livingston DM . (1999). Genes Dev 13: 64–75.

  • Braganca J, Eloranta JJ, Bamforth SD, Ibbitt JC, Hurst HC, Bhattacharya S . (2003). J Biol Chem 278: 16021–16029 (Epub 2003 Feb 12).

  • Braganca J, Swingler T, Marques FI, Jones T, Eloranta JJ, Hurst HC et al. (2002). J Biol Chem 277: 8559–8565 (Epub 2001 Dec 14).

  • Chen CR, Kang Y, Massague J . (2001). Proc Natl Acad Sci USA 98: 992–999.

  • Chipuk JE, Cornelius SC, Pultz NJ, Jorgensen JS, Bonham MJ, Kim SJ et al. (2002). J Biol Chem 277: 1240–1248.

  • Coussens LM, Tinkle CL, Hanahan D, Werb Z . (2000). Cell 103: 481–490.

  • Dennler S, Pendaries V, Tacheau C, Costas MA, Mauviel A, Verrecchia F . (2005). Oncogene 24: 1936–1945.

  • Dunwoodie SL, Rodriguez TA, Beddington RS . (1998). Mech Dev 72: 27–40.

  • Feng XH, Zhang Y, Wu RY, Derynck R . (1998). Genes Dev 12: 2153–2163.

  • Fox SB, Braganca J, Turley H, Campo L, Han C, Gatter KC et al. (2004). Cancer Res 64: 6075–6081.

  • Freedman SJ, Sun ZY, Kung AL, France DS, Wagner G, Eck MJ . (2003). Nat Struct Biol 10: 504–512.

  • Fridman R, Toth M, Chvyrkova I, Meroueh SO, Mobashery S . (2003). Cancer Metast Rev 22: 153–166.

  • Futaki S, Hayashi Y, Yamashita M, Yagi K, Bono H, Hayashizaki Y et al. (2003). J Biol Chem 278: 50691–50701.

  • Glenn DJ, Maurer RA . (1999). J Biol Chem 274: 36159–36167.

  • Gu Z, Kaul M, Yan B, Kridel SJ, Cui J, Strongin A et al. (2002). Science 297: 1186–1190.

  • Guo B, Inoki K, Isono M, Mori H, Kanasaki K, Sugimoto T et al. (2005). Kidney Int 68: 972–984.

  • Hayashi H, Abdollah S, Qiu Y, Cai J, Xu YY, Grinnell BW et al. (1997). Cell 89: 1165–1173.

  • Heussen C, Dowdle EB . (1980). Anal Biochem 102: 196–202.

  • Hiratsuka S, Nakamura K, Iwai S, Murakami M, Itoh T, Kijima H et al. (2002). Cancer Cell 2: 289–300.

  • Ilunga K, Nishiura R, Inada H, El-Karef A, Imanaka-Yoshida K, Sakakura T et al. (2004). Int J Exp Pathol 85: 373–379.

  • Itoh T, Tanioka M, Matsuda H, Nishimoto H, Yoshioka T, Suzuki R et al. (1999). Clin Exp Metast 17: 177–181.

  • Janknecht R, Wells NJ, Hunter T . (1998). Genes Dev 12: 2114–2119.

  • Javelaud D, Delmas V, Moller M, Sextius P, Andre J, Menashi S et al. (2005). Oncogene 24: 7624–7629.

  • Jonk LJ, Itoh S, Heldin CH, ten Dijke P, Kruijer W . (1998). J Biol Chem 273: 21145–21152.

  • Kang Y, Chen CR, Massague J . (2003). Mol Cell 11: 915–926.

  • Kranc KR, Bamforth SD, Braganca J, Norbury C, van Lohuizen M, Bhattacharya S . (2003). Mol Cell Biol 23: 7658–7666.

  • Leung MK, Jones T, Michels CL, Livingston DM, Bhattacharya S . (1999). Genomics 61: 307–313.

  • Luo X, Ding L, Xu J, Chegini N . (2005). Endocrinology 146: 1097–1118.

  • Lynch CC, Matrisian LM . (2002). Differentiation 70: 561–573.

  • Ma Z, Shah RC, Chang MJ, Benveniste EN . (2004). Mol Cell Biol 24: 5496–5509.

  • Massague J . (2000). Nat Rev Mol Cell Biol 1: 169–178.

  • Melchiori A, Allavena G, Bohm J, Remy W, Schmidt J, Parodi S et al. (1987). Anticancer Res 7: 475–479.

  • Nishihara A, Hanai J, Imamura T, Miyazono K, Kawabata M . (1999). J Biol Chem 274: 28716–28723.

  • Nishihara A, Hanai JI, Okamoto N, Yanagisawa J, Kato S, Miyazono K et al. (1998). Genes Cells 3: 613–623.

  • Ogawa K, Chen F, Kuang C, Chen Y . (2004). Biochem J 381: 413–422.

  • Okamoto T, Akaike T, Sawa T, Miyamoto Y, van der Vliet A, Maeda H . (2001). J Biol Chem 276: 29596–29602.

  • Pouponnot C, Jayaraman L, Massague J . (1998). J Biol Chem 273: 22865–22868.

  • Santibanez JF, Guerrero J, Quintanilla M, Fabra A, Martinez J . (2002). Biochem Biophys Res Commun 296: 267–273.

  • Sato H, Seiki M . (1993). Oncogene 8: 395–405.

  • Selvamurugan N, Fung Z, Partridge NC . (2002). FEBS Lett 532: 31–35.

  • Selvamurugan N, Kwok S, Alliston T, Reiss M, Partridge NC . (2004a). J Biol Chem 279: 19327–19334 (Epub 2004 Feb 24).

  • Selvamurugan N, Kwok S, Partridge NC . (2004b). J Biol Chem 279: 27764–27773 (E-pub 2004 Apr 14).

  • Shen X, Hu PP, Liberati NT, Datto MB, Frederick JP, Wang XF . (1998). Mol Biol Cell 9: 3309–3319.

  • Shi Y, Massague J . (2003). Cell 113: 685–700.

  • Shioda T, Fenner MH, Isselbacher KJ . (1996). PNAS 93: 12298–12303.

  • Shioda T, Fenner MH, Isselbacher KJ . (1997). Gene 204: 235–241.

  • Shioda T, Lechleider RJ, Dunwoodie SL, Li H, Yahata T, de Caestecker MP et al. (1998). Proc Natl Acad Sci USA 95: 9785–9790.

  • Sternlicht MD, Werb Z . (2001). Annu Rev Cell Dev Biol 17: 463–516.

  • Stroschein SL, Wang W, Zhou S, Zhou Q, Luo K . (1999). Science 286: 771–774.

  • Sun HB, Zhu YX, Yin T, Sledge G, Yang YC . (1998). Proc Natl Acad Sci USA 95: 13555–13560.

  • Sun Y, Liu X, Ng-Eaton E, Lodish HF, Weinberg RA . (1999). Proc Natl Acad Sci USA 96: 12442–12447.

  • Tardif G, Reboul P, Dupuis M, Geng C, Duval N, Pelletier JP et al. (2001). J Rheumatol 28: 1631–1639.

  • ten Dijke P, Hill CS . (2004). Trends Biochem Sci 29: 265–273.

  • ten Dijke P, Miyazono K, Heldin CH . (2000). Trends Biochem Sci 25: 64–70.

  • Tien ES, Davis JW, Vanden Heuvel JP . (2004). J Biol Chem 279: 24053–24063.

  • Tobin SW, Douville K, Benbow U, Brinckerhoff CE, Memoli VA, Arrick BA . (2002). Oncogene 21: 108–118.

  • Topper JN, DiChiara MR, Brown JD, Williams AJ, Falb D, Collins T et al. (1998). Proc Natl Acad Sci USA 95: 9506–9511.

  • Uria JA, Jimenez MG, Balbin M, Freije JM, Lopez-Otin C . (1998). J Biol Chem 273: 9769–9777.

  • Wakefield LM, Roberts AB . (2002). Curr Opin Genet Dev 12: 22–29.

  • Warner DR, Bhattacherjee V, Yin X, Singh S, Mukhopadhyay P, Pisano MM et al. (2004). Biochem Biophys Res Commun 324: 70–76.

  • Williams DA, Rosenblatt MF, Beier DR, Cone RD . (1988). Mol Cell Biol 8: 3864–3871.

  • Yahata T, de Caestecker MP, Lechleider RJ, Andriole S, Roberts AB, Isselbacher KJ et al. (2000). J Biol Chem 275: 8825–8834.

  • Yamamura Y, Hua X, Bergelson S, Lodish HF . (2000). J Biol Chem 275: 36295–36302.

  • Yin Z, Haynie J, Yang X, Han B, Kiatchoosakun S, Restivo J et al. (2002). Proc Natl Acad Sci USA 99: 10488–10493 (Epub 2002 Jul 29).

  • Yokota H, Goldring MB, Sun HB . (2003). J Biol Chem 278: 47275–47280.

  • Zhang Y, Feng XH, Derynck R . (1998). Nature 394: 909–913.

  • Zhang Y, Musci T, Derynck R . (1997). Curr Biol 7: 270–276.

  • Zimmerman CM, Padgett RW . (2000). Gene 249: 17–30.

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Acknowledgements

We are grateful to Dr David Donner for critical reading of manuscript; and Drs Edward Stavnezer, Paul MacDonald, and Monica Montano for helpful discussion and advice. This work was supported by grants from National Institute of Health (RO1 CA78433 to YCY).

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Authors and Affiliations

  1. Department of Pharmacology and Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Y-T Chou, H Wang, D Danielpour & Y-C Yang

  2. Department of Medical and Molecular Genetics, Indiana University School of Medicine and the Walther Cancer Institute, Indianapolis, IN, USA

    Y Chen

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  1. Y-T Chou
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  2. H Wang
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Correspondence to Y-C Yang.

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Chou, YT., Wang, H., Chen, Y. et al. Cited2 modulates TGF-β-mediated upregulation of MMP9. Oncogene 25, 5547–5560 (2006). https://doi.org/10.1038/sj.onc.1209552

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