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A role for E2F1 in Ras activation of p21(WAF1/CIP1) transcription

Abstract

We recently reported that E2F1 could transactivate the p21 promoter via cis-acting elements between −119 to +16 bp of the p21 gene. Here we show that activated V12-H-Ras can induce the p21 promoter through the same region of the p21 promoter by a p53-independent mechanism in NIH3T3 cells. In contrast, activated Ras was not able to induce the p21 promoter in E2F1−/− fibroblasts, suggesting that E2F1 is required for induction of the p21 promoter by activated Ras. Cotransfection of increasing concentrations of dominant negative E2F1 alone, or with dominant negative DP1 into NIH3T3 cells suppressed induction of the p21 promoter by activated Ras. These data suggest that p53-independent induction of the p21 promoter by activated Ras is mediated at least in part by E2F1.

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References

  • Adnane J, Bizouarn FA, Qian Y, Hamilton AD and Sebti SM. . 1998 Mol. Cell. Biol. 18: 6962–6970.

  • Aktas H, Cai H and Cooper GM. . 1997 Mol. Cell. Biol. 17: 3850–3857.

  • Albanese C, Johnson J, Watanabe G, Eklund N, Vu D, Arnold A and Pestell RG. . 1995 J. Biol. Chem. 270: 23589–23597.

  • Aziz N, Cherwinski H and McMahon M. . 1999 Mol. Cell. Biol. 19: 1101–1115.

  • Bates S, Phillips AC, Clark PA, Stott F, Peters G, Ludwig RL and Vousden KH. . 1998 Nature 395: 124–125.

  • Doetzlhofer A, Rotheneder H, Lagger G, Koranda M, Kurtev V, Brosch G, Wintersberger E and Seiser C. . 1999 Mol. Cell. Biol. 19: 5504–5511.

  • Dyson N. . 1998 Genes Dev. 12: 2245–2262.

  • El-Deiry W, Tokino T, Velculescu V, Levy D, Parsons R, Trent J, Lin D, Mercer WE, Kinzler K and Vogelstein B. . 1993 Cell 75: 817–825.

  • Fan J and Bertino JR. . 1997 Oncogene 14: 2595–2607.

  • Field SJ, Tsai FY, Kuo F, Zubiaga AM, Kaelin, Jr W, Livingston DM, Orkin SH and Greenberg ME. . 1996 Cell 85: 549–561.

  • Gartel AL, Goufman E, Tevosian SG, Shih H, Yee AS and Tyner AL. . 1998 Oncogene 17: 3463–3469.

  • Gartel AL and Tyner AL. . 1999 Exp. Cell Res. 246: 280–289.

  • Geng Y, Whoriskey W, Park MY, Bronson RT, Medema RH, Li T, Weinberg RA and Sicinski P. . 1999 Cell 97: 767–777.

  • Gjoerup O, Lukas J, Bartek J and Willumsen BM. . 1998 J. Biol. Chem. 273: 273, 18812–18818.

  • Gorman CM, Moffat L and Howard B. . 1982 Mol. Cell. Biol. 2: 1044–1051.

  • Halaban R, Cheng E, Zhang Y, Mandigo CE and Miglarese MR. . 1998 Oncogene 16: 2489–2501.

  • Harper JW, Elledge SJ, Keyomarsi K, Dynlacht B, Tsai L, Zhang P, Dobtowolski S, Bai C, Connell-Crowley L, Swindell E, Fox MP and Wei N. . 1995 Mol. Biol. Cell 6: 387–400.

  • Hiyama H, Lavarone A, LaBaer J and Reeves SA. . 1997 Oncogene 14: 2533–2542.

  • Hiyama H, Lavarone A and Reeves SA. . 1998 Oncogene 16: 1513–1523.

  • Johnson D, Cress W, Jakoi L and Nevins J. . 1994 Proc. Natl. Acad. Sci. USA 91: 12823–12827.

  • Kivinen L, Tsubari M, Haapajarvi T, Datto M, Wang X-F and Laiho M. . 1999 Oncogene 18: 6252–6261.

  • Liu Y, Martindale JL, Gorospe M and Holbrook NJ. . 1996 Cancer Res. 56: 31–35.

  • Lloyd AC, Obermuller F, Staddon S, Barth CF, McMahon M and Land H. . 1997 Genes Dev. 11: 663–677.

  • Lukas J, Herzinger T, Hansen K, Moroni MC, Resnitzky D, Helin K, Reed SI and Bartek J. . 1997 Genes Dev. 11: 1479–1492.

  • Lukas J, Petersen BO, Holm K, Bartek J and Helin K. . 1996 Mol. Cell. Biol. 16: 1047–1057.

  • Murray IA, Lewendon A, Williams JA, Cullin PM, Lashford AG and Shaw WV. . 1991 Nucleic Acids Res. 19: 6648.

  • Ohtani K, DeGregori J and Nevins JR. . 1995 Proc. Natl. Acad. Sci. USA 92: 12146–12150.

  • Olson MF, Paterson HF and Marshall CJ. . 1998 Nature 394: 295–299.

  • Palmero I, Pantoja C and Serrano M. . 1998 Nature 395: 125–126.

  • Pierce AM, Fisher SM, Conti CJ and Johnson DG. . 1998 Oncogene 16: 1267–1276.

  • Qin XQ, Livingston DM, Kaelin Jr W and Adams PD. . 1994 Proc. Natl. Acad. Sci. USA 91: 10918–10922.

  • Qiu RG, Chen J, McCormick F and Symons M. . 1995 Proc. Natl. Acad. Sci. USA 92: 11781–11785.

  • Schulze A, Zerfass K, Spitkovsky D, Henglein B and Jansen-Durr P. . 1994 Oncogene 9: 3475–3482.

  • Sellers WR, Rodgers JW and Kaelin Jr W. . 1995 Proc. Natl. Acad. Sci. USA 92: 11544–11548.

  • Serrano M, Lin AW, McCurrach ME, Beach D and Lowe SW. . 1997 Cell 88: 593–602.

  • Sewing A, Wiseman B, Lloyd AC and Land H. . 1997 Mol. Cell. Biol. 17: 5588–5597.

  • Wang ZM, Yang H and Livingston DM. . 1998 Proc. Natl. Acad. Sci. USA 95: 15583–15586.

  • Weintraub SJ, Chow KN, Luo RX, Zhang SH, He S and Dean DC. . 1995 Nature 375: 812–815.

  • Weintraub SJ, Prater CA and Dean DC. . 1992 Nature 358: 259–261.

  • Woods D, Parry D, Cherwinski H, Bosch E, Lees E and McMahon M. . 1997 Mol. Cell. Biol. 17: 5598–5611.

  • Wu CL, Classon M, Dyson N and Harlow E. . 1996 Mol. Cell. Biol. 16: 3698–3706.

  • Wu X and Levine AJ. . 1994 Proc. Natl. Acad. Sci. USA 91: 3602–3606.

  • Xu G, Livingston D and Krek W. . 1995 Proc. Natl. Acad. Sci. USA 92: 1357–1361.

  • Xu M, Sheppard KA, Peng CY, Yee AS and Piwnica-Worms H. . 1994 Mol. Cell. Biol. 14: 8420–8431.

  • Yamasaki L, Jacks T, Bronson R, Goillot E, Harlow E and Dyson NJ. . 1996 Cell 85: 537–548.

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Acknowledgements

This work was supported by American Cancer Society, Illinois Division #98-28 grant and a Charles E Culpeper Biomedical Pilot Initiative grant (AL Gartel) and NIH Grant DK48836 (AL Tyner). We thank Lili Yamasaki for E2F1−/− fibroblasts, Frank McCormick and Pablo Rodriguez-Viciana for the V12-H-Ras expression vector, Amy Yee for the dominant negative E2F1(1–282), Mary Classon for the dominant negative DP-1 (Δ103–126) and Martin McMahon for critical reading of the manuscript and valuable comments.

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Gartel, A., Najmabadi, F., Goufman, E. et al. A role for E2F1 in Ras activation of p21(WAF1/CIP1) transcription. Oncogene 19, 961–964 (2000). https://doi.org/10.1038/sj.onc.1203411

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