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  • Original Paper
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DNA damage-induced phosphorylation of p53 at serine 20 correlates with p21 and Mdm-2 induction in vivo

Abstract

We investigated the induction and physiological role of Ser20 phosphorylation of p53 in response to DNA damage caused by ionizing radiation (IR) or ultraviolet radiation (UV). A polyclonal antibody that specifically recognizes a p53 peptide containing phosphorylated Ser20 was generated and used to detect p53 phosphorylation at Ser20. Western blot analyses of p53 in four cell lines with this antibody revealed that the p53 protein was phosphorylated at Ser20 to a different extent after treatment with IR or UV. The phosphorylation of Ser20 of wild-type p53 correlated with enhanced induction of the p53 downstream target genes p21WAF1/Cip1 (p21) and mdm-2. These results suggest that DNA damage-induced phosphorylation of p53 at Ser20 enhances the transactivation function of p53 for p21 and mdm-2 in vivo.

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References

  • Ashcroft M, Kubbutat MHG and Vousden KH. . 1999 Mol. Cell. Biol. 19: 1751–1758.

  • Banin S, Moyal L, Khostravi R, Shieh SY, Taya Y, Anderson CW, Chessa L, Smorodinsky NI, Prives C, Shiloh Y and Ziv Y. . 1998 Science 281: 1674–1677.

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

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

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

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

  • Chen J, Wu X, Lin J and Levine AJ. . 1996 Mol. Cell. Biol. 16: 2445–2452.

  • Dumaz N, Milne DM and Meek DW. . 1999 FEBS Lett. 463: 312–316.

  • El-Deiry WS. . 1998 Cancer Biol. 8: 345–357.

  • Giaccia AJ and Kastan MB. . 1998 Genes Dev. 12: 2973–2983.

  • Gu J, Chen D, Rosenblum J, Rubin RM and Yuan Z-M. . 2000 Mol. Cell. Biol. 20: 1243–1253.

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

  • Higashimito Y, Saito S, Tong X-H, Hong A, Sakaguchi K, Appella A and Anderson CW. . 2000 J. Biol. Chem. 275: 23199–23203.

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

  • Honda R, Tanaka H and Yasuda H. . 1997 FEBS Lett. 420: 25–27.

  • Hsieh J-K, Chan FSG, O'Connor DJ, Mittnacht S, Zhong S and Lu X. . 1999 Mol. Cell 3: 181–193.

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

  • Kapoor M and Lozano G. . 1997 Proc. Natl. Acad. Sci. USA 95: 2834–2837.

  • Keller D, Zeng X, Li X, Kapoor M, Iordanov MS, Taya Y, Lozano G, Magun B and Lu H. . 1999 Biochem. Biophys. Res. Commun. 261: 464–471.

  • Ko LJ, Shieh SY, Chen X, Jayaraman L, Tamai K, Taya Y, Prives C and Pan ZQ. . 1997 Mol. Cell. Biol. 17: 7220–7229.

  • Kobayashi T, Ruan S, Jabbur JR, Consoli U, Clodi K, Shiku H, Owen-Schaub LB, Andreeff M, Reed JC and Zhang W. . 1998 Cell Death Differ. 5: 584–591.

  • Khosravi R, Maya R, Gottlieb T, Oren M, Shiloh Y and Shkedy D. . 1999 Proc. Natl. Acad. Sci. USA 96: 14973–14977.

  • Kubbatat MHG, Jones SN and Vousden KH. . 1997 Nature 387: 299–303.

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

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

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

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

  • Lu H, Taya Y, Ikeda M and Levine AJ. . 1998 Proc. Natl. Acad. Sci. USA 26: 6399–6402.

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

  • Meek DW, Simon S, Kikkawa U and Eckhart W. . 1990 EMBO J. 9: 3253–3260.

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

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

  • Prives C. . 1998 Cell 95: 5–8.

  • Sakaguchi K, Herrera JE, Saito S, Miki T, Bustin M, Vassilev A, Anderson CW and Appella E. . 1998 Genes Dev. 12: 2831–2841.

  • Sakaguchi K, Saito S, Higashimoto Y, Roy S, Anderson CW and Appella E. . 2000 J. Biol. Chem. 275: 9278–9283.

  • Sakaguchi K, Sakaguchi K, Sakamoto H, Lewis MS, Anderson CW, Erickson JW, Appella E and Xie D. . 1997 Biochemistry 36: 10117–10124.

  • Shieh S-Y, Ahn J, Tamai K, Taya Y and Prives C. . 2000 Genes Dev. 14: 289–300.

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

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

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

  • Tibbetts RS, Brunbaugh KM, Williams JM, Sarkaria JN, Cliby WA, Shieh SY, Prives C and Abraham RT. . 1999 Genes Dev. 13: 152–157.

  • Thut CJ, Chen JL, Klemin R and Tjian R. . 1995 Science 267: 100–104.

  • Uesugi M and Verdine GL. . 1999 Proc. Natl. Acad. Sci. USA 96: 14801–14806.

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

  • Watthew JF, Stavridi ES, Waterman JLF and Halazonetis TD. . 1998 Nat. Genet. 19: 175–178.

  • Woo RA, McLure KG, Lees-Miller SP, Rancourt DE and Lee PWK. . 1998 Nature 394: 700–704.

  • Wu X, Bayle JH, Olson D and Levine AJ. . 1993 Genes Dev. 7: 1126–1132.

  • Zhang W, Guo XY, Hu GY, Liu WB, Shay JW and Deisseroth AB. . 1994 EMBO J. 13: 2535–2544.

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Acknowledgements

We thank Drs Gigi Lozano, Paul Chiao, Raymond Meyn, Ralph Arlinghaus, Tse-Hua Tan, Elizabeth Grimm and Lei Li for their helpful discussions. We thank Lore Feldman for her editorial assistance. This work was supported in part by National Institutes of Health grants CA67987, CA55164 and CA77339. The MD Anderson sequencing core facility is supported by Core Grant CA16672. JR Jabbur was a recipient of the American Legion Auxiliary Fellowship.

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Jabbur, J., Huang, P. & Zhang, W. DNA damage-induced phosphorylation of p53 at serine 20 correlates with p21 and Mdm-2 induction in vivo. Oncogene 19, 6203–6208 (2000). https://doi.org/10.1038/sj.onc.1204017

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