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Comparative study of the p53-mdm2 and p53-MDMX interfaces

Oncogene volume 18, pages 189–199 (1999)Cite this article

Abstract

Mdm2 and MDMX are two structurally related p53-binding proteins which show the highest level of sequence similarity in the N-terminal p53-binding domains. Apart from its ability to inhibit p53 mediated transcription, a feature it shares with mdm2, very little is known about the physiological functions of MDMX. It is clearly distinct from mdm2 since its expression appears not to be regulated by p53 and it cannot compensate for lack of mdm2 in early development. We present data on the structural similarity between the p53 binding pockets of mdm2 and MDMX using p53- and phage-selected peptides. From the results we conclude that our recently devised innovative approach to reverse the mdm2-mediated inhibition of p53's transactivation function in vivo would probably target MDMX as well. Strategies for selectively targeting mdm2 and MDMX are suggested and a possible mechanism for regulating the p53-mdm2/MDMX interactions by protein phosphorylation is discussed.

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References

  • Barak Y and Oren M. . 1992 EMBO J. 11: 2115–2121.

  • Bartek J, Bartkova J, Lukas J, Staskova Z, Vojtesek B and Lane DP. . 1993 J. Pathol. 169: 27–34.

  • Blaydes JP, Gire V, Rowson JM and Wynford-Thomas D. . 1997 Oncogene 14: 1859–1868.

  • Böttger A, Böttger V, Garcia-Echeverria C, Chene P, Hochkeppel HK, Sampson W, Ang K, Howard SF, Picksley SM and Lane DP. . 1997a J. Mol. Biol. 269: 744–756.

  • Böttger A, Böttger V, Sparks A, Liu WL, Howard SF and Lane DP. . 1997b Curr. Biol. 7: 860–869.

  • Böttger V, Böttger A, Howard SF, Picksley SM, Chene P, Garcia Echeverria C, Hochkeppel HK and Lane DP. . 1996 Oncogene 13: 2141–2147.

  • Böttger V, Böttger A, Lane EB and Spruce BA. . 1995 J. Mol. Biol. 247: 932–946.

  • Cahilly Snyder L, Yang Feng T, Francke U and George DL. . 1987 Somat. Cell. Mol. Genet. 13: 235–244.

  • Chan S, Gabra H, Hill F, Evan G and Sikora K. . 1987 Mol. Cell Probes 1: 73–82.

  • Chen J, Marechal V and Levine AJ. . 1993 Mol. Cell Biol. 13: 4107–4114.

  • Fakharzadeh SS, Trusko SP and George DL. . 1991 EMBO J. 10: 1565–1569.

  • Fried LM, Koumenis C, Peterson SR, Green SL, van Zijl P, Allalunis-Turner J, Chen DJ, Fishel R, Giaccia AJ, Brown JM and Kirchgessner CU. . 1996 Proc. Natl. Acad. Sci. USA 93: 13825–13830.

  • Garcia-Echeverria C. . 1995a Lett. Pept. Sci. 2: 369–373.

  • Garcia-Echeverria C. . 1995b Lett. Pept. Sci. 2: 93–98.

  • Gottlieb TM and Jackson SP. . 1993 Cell 72: 131–142.

  • Haupt Y, Maya R, Kazaz A and Oren M. . 1997 Nature 387: 296–299.

  • Hoogenboom HR, Griffiths AD, Johnson KS, Chiswell DJ, Hudson P and Winter G. . 1991 Nucleic Acids Res. 19: 4133–4137.

  • Jones SN, Roe AE, Donehower LA and Bradley A. . 1995 Nature 378: 206–208.

  • Knippschild U, Milne D, Campbell L and Meek D. . 1996 Oncogene 13: 1387–1393.

  • Kubbutat MH, Jones SN and Vousden KH. . 1997 Nature 387: 299–303.

  • Kussie PH, Gorina S, Marechal V, Elenbaas B, Moreau J, Levine AJ and Pavletich NP. . 1996 Science 274: 948–953.

  • Lees-Miller SP, Sakaguchi K, Ullrich SJ, Appella E and Anderson CW. . 1992 Mol. Cell Biol. 12: 5041–5049.

  • Mayo LD, Turchi JJ and Berberich SJ. . 1997 Cancer Res. 57: 5013–5016.

  • McCafferty J, Fitzgerald KJ, Earnshaw J, Chiswell DJ, Link J, Smith R and Kenten J. . 1994 Appl. Biochem. Biotechnol. 47: 157–171.

  • Meek DW, Campbell LE, Jardine LJ, Knippschild U, McKendrick L and Milne DM. . 1997 Biochem. Soc. Trans. 25: 416–419.

  • Micheel B, Heymann S, Scharte G, Böttger V, Vogel F, Dubel S, Breitling F, Little M and Behrsing O. . 1994 J. Immunol. Methods 171: 103–109.

  • Midgley CA and Lane DP. . 1997 Oncogene 15: 1179–1189.

  • Milne DM, Palmer RH, Campbell DG and Meek DW. . 1992 Oncogene 7: 1361–1369.

  • Momand J, Zambetti GP, Olson DC, George D and Levine AJ. . 1992 Cell 69: 1237–1245.

  • Montes de Oca Luna R, Wagner DS and Lozano G. . 1995 Nature 378: 203–206.

  • Picksley SM, Vojtesek B, Sparks A and Lane DP. . 1994 Oncogene 9: 2523–2529.

  • Rathmell WK, Kaufmann WK, Hurt JC, Byrd LL and Chu G. . 1997 Cancer Res. 57: 68–74.

  • Shieh SY, Ikeda M, Taya Y and Prives C. . 1997 Cell 91: 325–334.

  • Shvarts A, Bazuine M, Dekker P, Ramos YF, Steegenga WT, Merckx G, van Ham RC, van der Houven van Oordt W, van der Eb AJ and Jochemsen AG. . 1997 Genomics 43: 34–42.

  • Shvarts A, Steegenga WT, Riteco N, van Laar T, Dekker P, Bazuine M, van Ham RC, van der Houven van Oordt W, Hateboer G, van der Eb AJ and Jochemsen AG. . 1996 EMBO J. 15: 5349–5357.

  • Stephen CW, Helminen P and Lane DP. . 1995 J. Mol. Biol. 248: 58–78.

  • Vojtesek B, Bartek J, Midgley CA and Lane DP. . 1992 J. Immunol. Methods 151: 237–244.

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Acknowledgements

We wish to thank Tristan Vaughan, Cambridge Antibody Technology Ltd., for the phagemid vector pCantab6. David P Lane is a Gibb Fellow of the Cancer Research Campaign. This work was funded by the Cancer Research Campaign and Novartis.

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Authors and Affiliations

  1. Cancer Research Campaign Laboratories, University of Dundee DD1, 4HN, Scotland, UK

    Volker Böttger, Angelika Böttger & David P Lane

  2. Department of Molecular Cell Biology, Laboratory of Molecular Carcinogenesis, Leiden University Medical Center, 2300 RA, Leiden, The Netherlands, PO Box 9503

    Yolande FM Ramos, Alex J van der Eb & Aart G Jochemsen

  3. Oncology Research, Novartis Pharma AG, CH-4002, Basel, Switzerland

    Carlos Garcia-Echeverria

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  1. Volker Böttger
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Böttger, V., Böttger, A., Garcia-Echeverria, C. et al. Comparative study of the p53-mdm2 and p53-MDMX interfaces. Oncogene 18, 189–199 (1999). https://doi.org/10.1038/sj.onc.1202281

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