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Involvement of p53 and Fas/CD95 in murine neural progenitor cell response to ionizing irradiation

Oncogene volume 23, pages 8497–8508 (2004)Cite this article

Abstract

We investigated the role of tumor suppressor p53 and Fas (CD95/APO-1), a member of the tumor necrosis factor receptor family, in neural progenitors response to γ-irradiation exposure. Telencephalic cells were obtained from wild-type C57Bl/6, or p53−/− or fas−/−, 15-day-old mouse embryos. They were cultured in conditions allowing neural progenitors to form proliferating clusters (neurospheres). A 2 Gy γ-irradiation induced a G1 cell cycle arrest and triggered apoptosis in wild-type neural progenitor cultures in correlation with an enhanced expression of p53 and of its downstream target p21WAF1, both of them acquiring a nuclear localization. These effects did not occur in p53−/− neural progenitors demonstrating the central role played by p53 in their response to ionizing radiation. Furthermore, the monoclonal antibody Jo2 directed against Fas induced apoptosis of wild type but not of fas−/− neural progenitors, indicating the existence of a functional Fas signaling pathway in neural progenitors. Ionizing radiation induced an increase of Fas membrane expression related to a p53-dependent increase of fas mRNA expression in wild-type neural progenitors. Moreover, fas−/− neural progenitors exhibited delayed radiation-induced apoptosis compared to wild-type cells. Therefore, these findings establish a role for Fas/CD95 related to p53 in the response of neural progenitors to γ-radiation exposure. Similar mechanisms could be triggered in neural progenitors in case of different stresses during brain development or in the course of various diseases affecting the adult brain.

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References

  • Adachi M, Suematsu S, Kondo T, Ogasawara J, Tanaka T, Yoshida N and Nagata S . (1995). Nat. Genet., 11, 294–300.

  • Armstrong J, Kaufman MH, Harrison DJ and Clarke AR . (1995). Curr. Biol., 5, 931–936.

  • Bargonetti J and Manfredi JJ . (2002). Curr. Opin. Oncol., 14, 86–91.

  • Becher B, D'Souza SD, Troutt AB and Antel JP . (1998). Neuroscience, 84, 627–634.

  • Belka C, Rudner J, Wesselborg S, Stepczynska A, Marini P, Lepple-Wienhues A, Faltin H, Bamberg M, Budach W and Schulze-Osthoff K . (2000). Oncogene, 19, 1181–1190.

  • Bennett M, Macdonald K, Chan SW, Luzio JP, Simari R and Weissberg P . (1998). Science, 282, 290–293.

  • Blaschke AJ, Staley K and Chun J . (1996). Development, 122, 1165–1174.

  • Blaschke AJ, Weiner JA and Chun J . (1998). J. Comp. Neurol., 396, 39–50.

  • Bouvard V, Zaitchouk T, Vacher M, Duthu A, Canivet M, Choisy-Rossi C, Nieruchalski M and May E . (2000). Oncogene, 19, 649–660.

  • Chao C, Saito S, Kang J, Anderson CW, Appella E and Xu Y . (2000). EMBO J., 19, 4967–4975.

  • Cheema ZF, Wade SB, Sata M, Walsh K, Sohrabji F and Miranda RC . (1999). J. Neurosci., 19, 1754–1770.

  • Chong MJ, Murray MR, Gosink EC, Russell HR, Srinivasan A, Kapsetaki M, Korsmeyer SJ and McKinnon PJ . (2000). Proc. Natl. Acad. Sci. USA, 97, 889–894.

  • Chow BM, Li YQ and Wong CS . (2000). Cell Death Differ., 7, 712–720.

  • Craig CG, Tropepe V, Morshead CM, Reynolds BA, Weiss S and van der Kooy D . (1996). J. Neurosci., 16, 2649–2658.

  • D'Sa-Eipper C, Leonard JR, Putcha G, Zheng TS, Flavell RA, Rakic P, Kuida K and Roth KA . (2001). Development, 128, 137–146.

  • Daniel PT and Krammer PH . (1994). J. Immunol., 152, 5624–5632.

  • Dhein J, Daniel PT, Trauth BC, Oehm A, Moller P and Krammer PH . (1992). J. Immunol., 149, 3166–3173.

  • Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery Jr CA, Butel JS and Bradley A . (1992). Nature, 356, 215–221.

  • Eischen CM, Kottke TJ, Martins LM, Basi GS, Tung JS, Earnshaw WC, Leibson PJ and Kaufmann SH . (1997). Blood, 90, 935–943.

  • Eizenberg O, Faber-Elman A, Gottlieb E, Oren M, Rotter V and Schwartz M . (1996). Mol. Cell. Biol., 16, 15178–15185.

  • Embree-Ku M, Venturini D and Boekelheide K . (2002). Biol. Reprod., 66, 1456–1461.

  • Engels IH, Stepczynska A, Stroh C, Lauber K, Berg C, Schwenzer R, Wajant H, Janicke RU, Porter AG, Belka C, Gregor M, Schulze-Osthoff K and Wesselborg S . (2000). Oncogene, 19, 4563–4573.

  • Felderhoff-Mueser U, Taylor DL, Greenwood K, Kozma M, Stibenz D, Joashi UC, Edwards AD and Mehmet H . (2000). Brain Pathol., 10, 17–29.

  • French LE, Hahne M, Viard I, Radlgruber G, Zanone R, Becker K, Muller C and Tschopp J . (1996). J. Cell Biol., 133, 335–343.

  • Fuchs EJ, McKenna KA and Bedi A . (1997). Cancer Res., 57, 2550–2554.

  • Fulda S, Scaffidi C, Pietsch T, Krammer PH, Peter ME and Debatin KM . (1998). Cell Death Differ., 5, 884–893.

  • Gao Y, Sun Y, Frank KM, Dikkes P, Fujiwara Y, Seidl KJ, Sekiguchi JM, Rathbun GA, Swat W, Wang J, Bronson RT, Malynn BA, Bryans M, Zhu C, Chaudhuri J, Davidson L, Ferrini R, Stamato T, Orkin SH, Greenberg ME and Alt FW . (1998). Cell, 95, 891–902.

  • Gutierrez del Arroyo A, Gil-Lamagniere C, Lazaro I, de Marco MC, Layunta I and Silva A . (2000). Oncogene, 19, 3647–3655.

  • Haik S, Gauthier LR, Granotier C, Peyrin JM, Lages CS, Dormont D and Boussin FD . (2000). Oncogene, 19, 2957–2966.

  • Harper JW, Adami GR, Wei N, Keyomarsi K and Elledge SJ . (1993). Cell, 75, 805–816.

  • Herzog KH, Chong MJ, Kapsetaki M, Morgan JI and McKinnon PJ . (1998). Science, 280, 1089–1091.

  • Huang HL, Fang LW, Lu SP, Chou CK, Luh TY and Lai MZ . (2003). Oncogene, 22, 8168–8177.

  • Jacks T, Remington L, Williams BO, Schmitt EM, Halachmi S, Bronson R and TWeinberg RA . (1994). Curr. Biol., 4, 1–7.

  • Johansson CB, Svensson M, Wallstedt L, Janson AM and Frisen J . (1999). Exp. Cell Res., 253, 733–736.

  • Johnson MD, Kinoshita Y, Xiang H, Ghatan S and Morrison RS . (1999). J. Neurosci., 19, 2996–3006.

  • Jordan J, Galindo MF, Prehn JH, Weichselbaum RR, Beckett M, Ghadge GD, Roos RP, Leiden JM and Miller RJ . (1997). J. Neurosci., 17, 1397–1405.

  • Komarova EA, Chernov MV, Franks R, Wang K, Armin G, Zelnick CR, Chin DM, Bacus SS, Stark GR and Gudkov AV . (1997). EMBO J., 16, 1391–1400.

  • Kovac AD, Grammig J, Mahlo J, Steiner B, Roth K, Nitsch R and Bechmann I . (2002). Eur. J. Neurosci., 16, 159–163.

  • Lee Y, Chong MJ and McKinnon PJ . (2001). J. Neurosci., 21, 6687–6693.

  • Levine AJ . (1997). Cell, 88, 323–331.

  • Liu X and Zhu XZ . (1999). Neuroreport, 10, 3087–3091.

  • Maecker HL, Koumenis C and Giaccia AJ . (2000). Cancer Res., 60, 4638–4644.

  • Martin-Villalba A, Herr I, Jeremias I, Hahne M, Brandt R, Vogel J, Schenkel J, Herdegen T and Debatin KM . (1999). J. Neurosci., 19, 3809–3817.

  • Matsui Y, Tsuchida Y and Keng PC . (2001). Am. J. Clin. Oncol., 24, 486–490.

  • May P and May E . (1999). Oncogene, 18, 7621–7636.

  • McKay R . (1997). Science, 276, 66–71.

  • Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P and Moll UM . (2003). Mol. Cell, 11, 577–590.

  • Miller FD, Pozniak CD and Walsh GS . (2000). Cell Death Differ., 7, 880–888.

  • Monje ML and Palmer T . (2003). Curr. Opin. Neurol., 16, 129–134.

  • Muller M, Strand S, Hug H, Heinemann EM, Walczak H, Hofmann WJ, Stremmel W, Krammer PH and Galle PR . (1997). J. Clin. Invest., 99, 403–413.

  • Muller M, Wilder S, Bannasch D, Israeli D, Lehlbach K, Li-Weber M, Friedman SL, Galle PR, Stremmel W, Oren M and Krammer PH . (1998). J. Exp. Med., 188, 2033–2045.

  • Munsch D, Watanabe-Fukunaga R, Bourdon JC, Nagata S, May E, Yonish-Rouach E and Reisdorf P . (2000). J. Biol. Chem., 275, 3867–3872.

  • Nagata S and Golstein P . (1995). Science, 267, 1449–1456.

  • Nat R, Radu E, Regalia T and Popescu LM . (2001). J. Cell. Mol. Med., 5, 417–428.

  • Newton K and Strasser A . (2000). J. Exp. Med., 191, 195–200.

  • Nishimura Y, Hirabayashi Y, Matsuzaki Y, Musette P, Ishii A, Nakauchi H, Inoue T and Yonehara S . (1997). Int. Immunol., 9, 307–316.

  • Norimura T, Nomoto S, Katsuki M, Gondo Y and Kondo S . (1996). Nat. Med., 2, 577–580.

  • O'Connor L, Harris AW and Strasser A . (2000). Cancer Res., 60, 1217–1220.

  • Oppenheim RW . (1991). Annu. Rev. Neurosci., 14, 453–501.

  • Owen-Schaub LB, Zhang W, Cusack JC, Angelo LS, Santee SM, Fujiwara T, Roth JA, Deisseroth AB, Zhang WW, Kruzel E and Radinski R . (1995). Mol. Cell. Biol., 15, 3032–3040.

  • Park C, Sakamaki K, Tachibana O, Yamashima T, Yamashita J and Yonehara S . (1998). Biochem. Biophys. Res. Commun., 252, 623–628.

  • Peissner W, Kocher M, Treuer H and Gillardon F . (1999). Brain Res. Mol. Brain Res., 71, 61–68.

  • Rakic S and Zecevic N . (2000). Eur. J. Neurosci., 12, 2721–2734.

  • Rao MS . (1999). Anat. Rec., 257, 137–148.

  • Raoul C, Henderson CE and Pettmann B . (1999). J. Cell Biol., 147, 1049–1062.

  • Reap EA, Roof K, Maynor K, Borrero M, Booker J and Cohen PL . (1997). Proc. Natl. Acad. Sci. USA, 94, 5750–5755.

  • Roos W, Baumgartner M and Kaina B . (2004). Oncogene, 23, 359–367.

  • Saas P, Walker PR, Hahne M, Quiquerez AL, Schnuriger V, Perrin G, French L, Van Meir EG, de Tribolet N, Tschopp J and Diatri PY . (1997). J. Clin. Invest., 99, 1173–1178.

  • Sah VP, Attardi LD, Mulligan GJ, Williams BO, Bronson RT and Jacks T . (1995). Nat. Genet., 10, 175–180.

  • Sheard MA . (2001). Int. J. Cancer, 96, 213–220.

  • Slack RS, Belliveau DJ, Rosenberg M, Atwal J, Lochmuller H, Aloyz R, Haghighi A, Lach B, Seth P, Cooper E and Miller FD . (1996). J. Cell Biol., 135, 1085–1096.

  • Strasser-Wozak EM, Hartmann BL, Geley S, Sgonc R, Bock G, Santos AJ, Hattmannstorfer R, Wolf H, Pavelka M and Kofler R . (1998). Cell Death Differ., 5, 687–693.

  • Tada E, Parent JM, Lowenstein DH and Fike JR . (2000). Neuroscience, 99, 33–41.

  • Thomaidou D, Mione MC, Cavanagh JF and Parnavelas JG . (1997). J. Neurosci., 17, 1075–1085.

  • Timmer T, de Vries EG and de Jong S . (2001). J. Pathol., 196, 125–134.

  • Uberti D, Piccioni L, Cadei M, Grigolato P, Rotter V and Memo M . (2001). Brain Res. Mol. Brain Res., 93, 81–89.

  • Uchida N, Buck DW, He D, Reitsma MJ, Masek M, Phan TV, Tsukamoto AS, Gage FH and Weissman IL . (2000). Proc. Natl. Acad. Sci. USA, 97, 14720–14725.

  • Unger C, Buchmann A, Bunemann CL, Kress S and Schwarz M . (1998). Cell Death Differ., 5, 87–95.

  • von Haefen C, Wieder T, Essmann F, Schulze-Osthoff K, Dorken B and Daniel PT . (2003). Oncogene, 22, 2236–2247.

  • Waldman T, Kinzler KW and Vogelstein B . (1995). Cancer Res., 55, 5187–5190.

  • Xiang H, Kinoshita Y, Knudson CM, Korsmeyer SJ, Schwartzkroin PA and Morrison RS . (1998). J. Neurosci., 18, 1363–1373.

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Acknowledgements

We thank Catherine Chapel, Gaëlle Pennarun, Olivier Etienne, Christine Granotier, Patrick Flament and Willy Hélière for their technical assistance. This work was supported by grants of Electricité de France (EDF) and the Association pour la Recherche contre le Cancer (ARC).

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  1. Alexandra Semont and Ewa B Nowak: Both these authors contributed equally to this work

Authors and Affiliations

  1. Laboratoire de RadioPathologie, DRR/DSV, CEA, IPSC, Fontenay-aux-Roses, France

    Alexandra Semont, Ewa B Nowak, Céline Silva Lages, Céline Mathieu, Marc-André Mouthon, Pascal Millet & François D Boussin

  2. Laboratoire de Cancérogenèse Moléculaire, UMR217 DRR/DSV, CEA-CNRS, Fontenay-aux-Roses, France

    Evelyne May

  3. Laboratoire de Radiosensibilité des cellules germinales, SEGG/DRR/DSV, CEA, IPSC, Fontenay-aux-Roses, France

    Isabelle Allemand

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Semont, A., Nowak, E., Silva Lages, C. et al. Involvement of p53 and Fas/CD95 in murine neural progenitor cell response to ionizing irradiation. Oncogene 23, 8497–8508 (2004). https://doi.org/10.1038/sj.onc.1207821

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