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Role of MAP kinases in UVB-induced phosphorylation of p53 at serine 20

Oncogene volume 21, pages 1580–1589 (2002)Cite this article

Abstract

Phosphorylation of the p53 tumor suppressor protein is one of the key regulatory steps in its activation process. Serine 20 phosphorylation of p53 has been shown to be required for the activation of p53 following UV radiation, but the signaling pathway mediating UV-induced phosphorylation is unknown. Here, we determined the role of MAP kinases in UVB-induced phosphorylation and found that JNKs are directly involved in the phosphorylation of p53 at serine 20. In a mouse JB6 epidermal cell line, dominant negative JNK1 abrogated UVB-induced phosphorylation of p53 at serine 20, whereas dominant negative p38 kinase or its inhibitor, SB202190, partially attenuated the phosphorylation. In contrast, dominant negative ERK2 or the MEK1 inhibitor, PD98059, had no effect on p53 phosphorylation at serine 20. Importantly, UVB-activated or active recombinant JNK1/2, or the p38 kinase downstream target, MAPKAPK-2, but not ERKs or p38 kinase, phosphorylated p53 at serine 20 in vitro. Furthermore, phosphorylation of p53 at serine 20 by UVB-activated JNKs and UVB-induced p53-dependent transcriptional activity were suppressed in Jnk1 or Jnk2 knockout (Jnk1−/− or Jnk2−/−) cells. Additionally, Jnk1−/−, Jnk2−/−, and p53-deficient (p53−/−) cells, as well as re-introduction of a p53 mutant with substitution of serine 20 to alanine into p53−/− cells, were defective for UVB-induced apoptosis. These findings strongly suggest that JNKs are the major direct signaling mediators of UVB-induced p53 phosphorylation at serine 20.

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References

  • Adler V, Pincus MR, Brandt-Rauf PW, Ronai Z . 1995 Proc. Natl. Acad. Sci. USA 92: 10585–10589

  • Adler V, Pincus MR, Polotskaya A, Montano X, Friedman FK, Ronai Z . 1996 J. Biol. Chem. 271: 23304–23309

  • Adler V, Pincus MR, Minamoto T, Fuchs SY, Bluth MJ, Brandt-Rauf PW, Friedman FK, Robinson RC, Chen JM, Wang XW, Harris CC, Ronai Z . 1997 Proc. Natl. Acad. Sci. USA 94: 1686–1691

  • Agarwal ML, Taylor WR, Chernov MV, Chernova OB, Stark GR . 1998 J. Biol. Chem. 273: 1–4

  • Alessi DR, Cuenda A, Cohen P, Dudley DT, Saltiel AR . 1995 J. Biol. Chem. 270: 27489–27494

  • Bulavin DV, Saito S, Hollander MC, Sakaguchi K, Anderson CW, Appella E, Fornace AJ . 1999 EMBO J. 18: 6845–6854

  • Canman CE, Lim DS, Cimprich KA, Taya Y, Tamai K, Sakaguchi K, Appella E, Kastan MB, Siliciano JD . 1998 Science 281: 1677–1679

  • Chehab NH, Malikzay A, Appel M, Halazonetis TD . 2000 Genes Dev. 14: 278–288

  • Chehab NH, Malikzay A, Stavridi ES, Halazonetis TD . 1999 Proc. Natl. Acad. Sci. USA 96: 13777–13782

  • Chen N, Ma WY, Huang C, Dong Z . 1999 J. Biol. Chem. 274: 15389–15394

  • Chen YR, Wang X, Templeton D, Davis RJ, Tan TH . 1996 J. Biol. Chem. 271: 31929–31936

  • Derijard B, Hibi M, Wu IH, Barrett T, Su B, Deng T, Karin M, Davis RJ . 1994 Cell 76: 1025–1037

  • Dhanasekaran N, Premkumar Reddy E . 1998 Oncogene 17: 1447–1455

  • Dong C, Yang DD, Wysk M, Whitmarsh AJ, Davis RJ, Flavell RA . 1998 Science 282: 2092–2095

  • Dumaz N, Meek DW . 1999 EMBO J. 18: 7002–7010

  • el-Deiry WS, Kern SE, Pietenpol JA, Kinzler KW, Vogelstein B . 1992 Nat. Genet. 1: 45–49

  • Fritsche M, Haessler C, Brandner G . 1993 Oncogene 8: 307–318

  • Frost JA, Geppert TD, Cobb MH, Feramisco JR . 1994 Proc. Natl. Acad. Sci. USA 91: 3844–3848

  • Fuchs SY, Adler V, Buschmann T, Yin Z, Wu X, Jones SN, Ronai Z . 1998a Genes Dev. 12: 2658–2663

  • Fuchs SY, Adler V, Pincus MR, Ronai Z . 1998b Proc. Natl. Acad. Sci. USA 95: 10541–10546

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

  • Hazzalin CA, Cano E, Cuenda A, Barratt MJ, Cohen P, Mahadevan LC . 1996 Curr. Biol. 6: 1028–1031

  • Hirao A, Kong YY, Matsuoka S, Wakeham A, Ruland J, Yoshida H, Liu D, Elledge SJ, Mak TW . 2000 Science 287: 1824–1827

  • Hu MC, Qiu WR, Wang YP . 1997 Oncogene 15: 2277–2287

  • Huang C, Ma W, Bowden GT, Dong Z . 1996a J. Biol. Chem. 271: 31262–31268

  • Huang C, Ma WY, Dong Z . 1996b Mol. Cell. Biol. 16: 6427–6435

  • Huang C, Ma WY, Ryan CA, Dong Z . 1997 Proc. Natl. Acad. Sci. USA 94: 11957–11962

  • Huang C, Ma WY, Young MR, Colburn N, Dong Z . 1998 Proc. Natl. Acad. Sci. USA 95: 156–161

  • Huang C, Ma WY, Maxiner A, Sun Y, Dong Z . 1999a J. Biol. Chem. 274: 12229–12235

  • Huang C, Li JX, Ma WY, Dong ZG . 1999b J. Biol. Chem. 274: 29672–29676

  • Kapoor M, Lozano G . 1998 Proc. Natl. Acad. Sci. USA 95: 2834–2837

  • Kastan MB, Radin AI, Kuerbitz SJ, Onyekwere O, Wolkow CA, Civin CI, Stone KD, Woo T, Ravindranath Y, Craig RW . 1991 Cancer Res. 51: 4279–4286

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

  • Lambert PF, Kashanchi F, Radonovich MF, Shiekhattar R, Brady JN . 1998 J. Biol. Chem. 273: 33048–33053

  • Levine AJ . 1997 Cell 88: 323–331

  • Livingstone LR, White A, Sprouse J, Livanos E, Jacks T, Tlsty TD . 1992 Cell 70: 923–935

  • Loo DT, Cotman CW . 1994 Cell Biology: A Laboratory Handbook Celis JE (ed) San Diego, CA: Academic Press Inc pp 45–53

    Google Scholar 

  • Lowe SW, Schmitt EM, Smith SW, Osborne BA, Jacks T . 1993 Nature 362: 847–849

  • Lu H, Taya Y, Ikeda M, Levine AJ . 1998 Proc. Natl. Acad. Sci. USA 95: 6399–6402

  • Maki CG, Howley PM . 1997 Mol. Cell. Biol. 17: 355–363

  • Merritt AJ, Potten CS, Kemp CJ, Hickman JA, Balmain A, Lane DP, Hall PA . 1994 Cancer Res. 54: 614–617

  • Milne DM, Campbell LE, Campbell DG, Meek DW . 1995 J. Biol. Chem. 270: 5511–5518

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

  • Nomura M, Kaji A, Ma WY, Zhong S, Liu G, Bowden GT, Miyamoto K, Dong Z . 2001 J. Biol. Chem. 276: 25558–25567

  • Oliner JD, Pietenpol JA, Thiagalingam S, Gyuris J, Kinzler KW, Vogelstein B . 1993 Nature 362: 857–860

  • Prives C, Hall PA . 1999 J. Pathol. 187: 112–126

  • Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ . 1995 J. Biol. Chem. 270: 7420–7426

  • Rincon M, Enslen H, Raingeaud J, Recht M, Zapton T, Su MS, Penix LA, Davis RJ, Flavell RA . 1998 EMBO J. 17: 2817–2829

  • She QB, Chen N, Dong Z . 2000 J. Biol. Chem. 275: 20444–20449

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

  • Shieh SY, Taya Y, Prives C . 1999 EMBO J. 18: 1815–1823

  • Siliciano JD, Canman CE, Taya Y, Sakaguchi K, Appella E, Kastan MB . 1997 Genes Dev. 11: 3471–3481

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

  • Unger T, Juven-Gershon T, Moallem E, Berger M, Vogt, Sionov R, Lozano G, Oren M, Haupt Y . 1999a EMBO J. 18: 1805–1814

  • Unger T, Sionov RV, Moallem E, Yee CL, Howley PM, Oren M, Haupt Y . 1999b Oncogene 18: 3205–3212

  • Watts RG, Huang C, Young MR, Li JJ, Dong Z, Pennie WD, Colburn NH . 1998 Oncogene 17: 3493–3498

  • Yang DD, Conze D, Whitmarsh AJ, Barrett T, Davis RJ, Rincon M, Flavell RA . 1998 Immunity 9: 575–585

  • Zhang YG, Zhong SP, Dong ZM, Chen NY, Bode AM, Ma WY, Dong ZG . 2001 J. Biol. Chem. 276: 14572–14580

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Acknowledgements

We thank Dr Ann M Bode for critical reading of the manuscript; Ms Andria Hansen for secretarial assistance; Dr Richard A Flavell for providing WT, Jnk1−/− and Jnk2−/− mice; Dr Tyler Jacks for providing p53+/+ and p53−/− MEFs; and Dr Thanos D Halazonetis for providing wt p53 and mutant p53 S20A. This work was supported by The Hormel Foundation and National Institutes of Health grant CA 77646.

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  1. The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, 55912, Minnesota, MN, USA

    Qing-Bai She, Wei-Ya Ma & Zigang Dong

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Correspondence to Zigang Dong.

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She, QB., Ma, WY. & Dong, Z. Role of MAP kinases in UVB-induced phosphorylation of p53 at serine 20. Oncogene 21, 1580–1589 (2002). https://doi.org/10.1038/sj.onc.1205239

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