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  • Original Paper
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Several regions of p53 are involved in repression of RNA polymerase III transcription

Abstract

The tumour suppressor p53 has been shown to regulate RNA polymerase (pol) III transcription both in vitro and in vivo. We have characterized the regions of p53 that contribute to this effect. Repression of pol III transcription in vivo does not require residues 13–19 near the N-terminus of p53 that are highly conserved through evolution. However, amino acids 22 and 23 in the adjacent transactivation domain do contribute to the inhibition of pol III activity. Deletions within the central DNA-binding core domain (residues 102–292) of p53 can entirely abolish the repression function in these assays, despite the fact that pol III templates contain no recognized p53 binding site. Deletion or substitution within the C-terminal domain of p53 can also compromise its ability to repress pol III activity in vitro and in transfected cells. These observations reveal that repression of pol III transcription is a complex function involving multiple regions of p53 extending throughout much of the protein.

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References

  • Abelson HT, Johnson LF, Penman S, Green H . 1974 Cell 1: 161–165

  • Avantaggiati ML, Ogryzko V, Gardner K, Giordano A, Levine AS, Kelly K . 1997 Cell 89: 1175–1184

  • Brown TRP, Scott PH, Stein T, Winter AG, White RJ . 2000 Gene Expr. 9: 15–28

  • Cairns CA, White RJ . 1998 EMBO J. 17: 3112–3123

  • Chang J, Kim DH, Lee SW, Choi KY, Sung YC . 1995 J. Biol. Chem. 270: 25014–25019

  • Chen KV, Ueda K, Pastan I, Gottesman MM . 1992 Science 255: 459–462

  • Chesnokov I, Chu WM, Botchan MR, Schmid CW . 1996 Mol. Cell. Biol. 16: 7084–7088

  • Cox LS, Lane DP . 1995 Bioessays 17: 501–508

  • Crook T, Marston NJ, Sara EA, Vousden KH . 1994 Cell 79: 817–827

  • Dean N, Berk AJ . 1988 Mol. Cell. Biol. 8: 3017–3025

  • El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B . 1993 Cell 75: 817–825

  • Farmer G, Bargonetti J, Zhu H, Friedman P, Prywes R, Prives C . 1992 Nature 358: 83–86

  • Farmer G, Colgan J, Nakatani Y, Manley JL, Prives C . 1996a Mol. Cell. Biol. 16: 4295–4304

  • Farmer G, Friedlander P, Colgan J, Manley JL, Prives C . 1996b Nucleic Acids Res. 24: 4281–4288

  • Fields S, Jang SK . 1990 Science 249: 1046–1049

  • Ginsberg D, Mechta F, Yaniv M, Oren M . 1991 Proc. Natl. Acad. Sci. USA 88: 9979–9983

  • Hollstein M, Rice K, Greenblatt MS, Soussi T, Fucks R, Sorlie T, Hovig E, Smith-Sorensen B, Montesano R, Harris CC . 1994 Nucleic Acids Res. 22: 3551–3555

  • Hollstein M, Sidransky D, Vogelstein B, Harris CC . 1991 Science 253: 49–53

  • Hong T-M, Chen JJW, Peck K, Yang P-C, Wu C-W . 2001 J. Biol. Chem. 276: 1510–1515

  • Horikoshi N, Usheva A, Chen J, Levine AJ, Weinmann R, Shenk T . 1995 Mol. Cell. Biol. 15: 227–234

  • Hupp TR, Meek DW, Midgley CA, Lane DP . 1992 Cell 71: 875–886

  • Jeffrey PD, Gorina S, Pavletich NP . 1995 Science 267: 1498–1502

  • Kassavetis GA, Joazeiro CAP, Pisano M, Geiduschek EP, Colbert T, Hahn S, Blanco JA . 1992 Cell 71: 1055–1064

  • Kern S, Kinzler K, Bruskin A, Jarosz D, Friedman P, Prives C, Vogelstein B . 1991 Science 252: 1708–1711

  • Ko LJ, Prives C . 1996 Genes Dev. 10: 1054–1072

  • Kubbutat MHG, Ludwig RL, Ashcroft M, Vousden KH . 1998 Mol. Cell. Biol. 18: 5690–5698

  • Levine AJ . 1997 Cell 88: 323–331

  • Lin J, Chen J, Elenbaas B, Levine AJ . 1994 Genes Dev. 8: 1235–1246

  • Lobo SM, Tanaka M, Sullivan ML, Hernandez N . 1992 Cell 71: 1029–1040

  • Lu H, Levine AJ . 1995 Proc. Natl. Acad. Sci. USA 92: 5154–5158

  • Mack DH, Vartikar J, Pipas JM, Laimins LA . 1993 Nature 363: 281–283

  • Marston NJ, Ludwig RL, Vousden KH . 1998 Oncogene 16: 3123–3131

  • Mauck JC, Green H . 1974 Cell 3: 171–177

  • Molinari M, Okorokov AL, Milner J . 1996 Oncogene 13: 2077–2086

  • Murphy M, Ahn J, Walker KK, Hoffman WH, Evans RM, Levine AJ, George DL . 1999 Genes Dev. 13: 2490–2501

  • Murphy M, Hunman A, Levine AJ . 1996 Genes Dev. 10: 2971–2980

  • Neufeld TP, Edgar BA . 1998 Curr. Opin. Cell. Biol. 10: 784–790

  • Okorokov AL, Milner J . 1999 Mol. Cell. Biol. 19: 7501–7510

  • Okorokov AL, Ponchel F, Milner J . 1997 EMBO J. 16: 6008–6017

  • Paule MR, White RJ . 2000 Nucleic Acids Res. 28: 1283–1298

  • Pietenpol JA, Tokino T, Thiagalingam S, El-Deiry WS, Kinzler KW, Vogelstein BS . 1994 Proc. Natl. Acad. Sci. USA 91: 1998–2002

  • Ragimov N, Krauskopf A, Navot N, Rotter V, Oren M, Aloni Y . 1993 Oncogene 8: 1183–1193

  • Raycroft L, Wu H, Lozano G . 1990 Science 249: 1049–1051

  • Sang B-C, Chen J-Y, Minna J, Barbosa MS . 1994 Oncogene 9: 853–859

  • Scott PH, Cairns CA, Sutcliffe JE, Alzuherri HM, Mclees A, Winter AG, White RJ . 2001 J. Biol. Chem. 276: 1005–1014

  • Seto E, Usheva A, Zambetti GP, Momand J, Horikoshi N, Weinmann R, Levine AJ, Shenk T . 1992 Proc. Natl. Acad. Sci. USA 89: 12028–12032

  • Shen Y, Shenk T . 1994 Proc. Natl. Acad. Sci. USA 91: 8940–8944

  • Shew J-Y, Lin BT-Y, Chen P-L, Tseng BY, Yang-Feng TL, Lee W-H . 1990 Proc. Natl. Acad. Sci. USA 87: 6–10

  • Simmen KA, Bernues J, Lewis JD, Mattaj IW . 1992 Nucleic Acids Res. 20: 5889–5898

  • Sionov RV, Haupt Y . 1999 Oncogene 18: 6145–6157

  • Soussi T, Caron de Fromentel C, May P . 1990 Oncogene 5: 945–952

  • Stein T, Crighton D, Boyle JM, Varley JM, White RJ . 2002 Oncogene 21: 2961–2970

  • Sturzbecher HW, Brain R, Addison C, Rudge K, Remm M, Grimaldi M, Kennan E, Jenkins JR . 1992 Oncogene 7: 1513–1523

  • Subler MA, Martin DW, Deb S . 1994 Oncogene 9: 1351–1359

  • Sutcliffe JE, Brown TRP, Allison SJ, Scott PH, White RJ . 2000 Mol. Cell. Biol. 20: 9192–9202

  • Taggart AKP, Fisher TS, Pugh BF . 1992 Cell 71: 1015–1028

  • Thut CJ, Chen J-L, Klemm R, Tjian R . 1995 Science 267: 100–104

  • Vogelstein B, Lane D, Levine AJ . 2000 Nature 408: 307–310

  • Vousden KH . 2000 Cell 103: 691–694

  • White RJ . 1998a RNA Polymerase III Transcription Berlin: Springer-Verlag

    Book  Google Scholar 

  • White RJ . 1998b Int. J. Oncol. 12: 741–748

  • White RJ, Gottlieb TM, Downes CS, Jackson SP . 1995a Mol. Cell. Biol. 15: 6653–6662

  • White RJ, Gottlieb TM, Downes CS, Jackson SP . 1995b Mol. Cell. Biol. 15: 1983–1992

  • White RJ, Jackson SP . 1992 Cell 71: 1041–1053

  • White RJ, Stott D, Rigby PWJ . 1989 Cell 59: 1081–1092

  • White RJ, Trouche D, Martin K, Jackson SP, Kouzarides T . 1996 Nature 382: 88–90

  • Yu J, Zhang L, Hwang PM, Rago C, Kinzler KW, Vogelstein B . 1999 Proc. Natl. Acad. Sci. USA 96: 14517–14522

  • Zambetti G, Bargonetti J, Walker K, Prives C, Levine A . 1992 Genes Dev. 6: 1143–1152

  • Zhao R, Gish K, Murphy M, Yin Y, Notterman D, Hoffman WH, Tom E, Mack DH, Levine AJ . 2000 Genes Dev. 14: 981–993

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Acknowledgements

We wish to thank Arnold Berk, Sheila Graham, Arnold Levine and Karen Vousden for plasmids. This work was funded by Yorkshire Cancer Research to J Milner and by project grant SP2314/0102 to RJ White from Cancer Research UK (formerly the Cancer Research Campaign). RJ White is a Jenner Research Fellow of the Lister Institute of Preventive Medicine.

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Correspondence to Robert J White.

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Stein, T., Crighton, D., Warnock, L. et al. Several regions of p53 are involved in repression of RNA polymerase III transcription. Oncogene 21, 5540–5547 (2002). https://doi.org/10.1038/sj.onc.1205739

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  • DOI: https://doi.org/10.1038/sj.onc.1205739

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