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Role of protein kinase C and the Sp1-p53 complex in activation of p21WAF-1 expression by 12-O-tetradecanoylphorbol-13-acetate in human T cells

Oncogene volume 22, pages 5315–5324 (2003)Cite this article

Abstract

Previous reports have shown that, in certain cell types, p21WAF-1, which plays a central role in cell proliferation, can be activated by HTLV-I Tax protein and by TPA. Tax and TPA are also known to stimulate HTLV-I gene expression. Since cell proliferation has a major impact on HTLV-I replication, it was of interest to investigate their effect on p21WAF-1 in human T cells, which are the main target of HTLV-I in human infection. This study demonstrates that p21WAF-1 is activated in such cells by both factors, each acting through a different mechanism that does not influence the other. The effect of TPA is shown to require PKC activity. Notably, however, examination of different PKC isoforms revealed that PKC-α and PKC-ɛ stimulated p21WAF-1 expression, whereas PKC-η was rather inhibitory and PKC-β1 and β2 were ineffective. All these isoforms were found to be activated by TPA in the employed T cells, but this apparent paradox was resolved by the observation that when coexpressed together in these cells, the stimulatory PKCs override the inhibitory isoform. Further experiments demonstrated that the PKC-induced p21WAF-1 activation was mediated by binding of Sp1-p53 complex to the second most upstream of the six Sp1 recognition sites present in its promoter and that this effect did not require the cooperation of an p53-binding site.

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References

  • Bellido T, O'brien CA, Roberson PK and Manolagas SC . (1998). J. Biol. Chem., 273, 21137–21144.

  • Biggs JR and Kraft AS . (1999). J. Biol. Chem., 274, 36987–36994.

  • Biggs JR, Kudlow JE and Kraft AS . (1996). J. Biol. Chem., 271, 901–906.

  • Billon N, van Grunsven LA and Rudkin BB . (1996). Oncogene, 13, 2047–2054.

  • Blatt NB and Glick GD . (2001). Bioorg. Biomed. Chem., 9, 1371–1384.

  • Boulaire J, Fotedar A and Fotedar R . (2000). Pathol. Biol. (Paris), 48, 190–202.

  • Cereseto A, Diella F, Mulloy JC, Cara A, Michaeli P, Grassmann R, Franchini G and Klotman ME . (1996). Blood, 88, 1551–1560.

  • Cheng J and Haas M . (1990). Mol. Cell. Biol., 10, 5502–5509.

  • Datto MB, Yu Y and Wang XF . (1995). J. Biol. Chem., 270, 28623–28628.

  • de La Fuente C, Satiago F, Chong SY, Deng L, Mayhood T, Fu P, Stein D, Denny T, Coffman F, Azimi N, Mahieux R and Kashanchi F . (2000). J. Virol., 74, 7270–7283.

  • Decker SJ . (1995). J. Biol. Chem., 270, 30841–30844.

  • Dempsey EC, Newton AC, Mochly-Rosen D, Fields AP, Reyland ME, Insel PA and Messing RO . (2000). Am. J. Physiol. Lung Cell Mol. Physiol., 279, L429–L438.

  • Eldar E, Zisman Y, Ullrich A and Livneh E . (1990). J. Biol. Chem., 265, 13290–13296.

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

  • Gartel AL and Tyner AL . (1999). Exp. Cell Res., 246, 280–289.

  • Gervais JLM, Seth P and Zhang H . (1998). J. Biol. Chem., 273, 19207–19212.

  • Gitlin SD, Lindholm PF, Marriott SJ and Brady JN . (1991). J. Virol., 65, 2612–2621.

  • Gorospe M, Cirielli C, Wang X, Seth P, Capogrossi MC and Holbrook NJ . (1997). Oncogene, 14, 929–935.

  • Gorospe M, Wang X, Guyton KZ and Holbrook NJ . (1996). Mol. Cell. Biol., 16, 6654–6660.

  • Gorospe M, Wang X and Hollbrook NJ . (1998). Mol. Cell. Biol., 18, 1400–1407.

  • Gorospe M, Wang X and Holbrook NJ . (1999). Gene Expression, 7, 377–385.

  • Gualberto A and Balwin ASJ . (1955). J. Biol. Chem., 270, 19680–19683.

  • Gualberto A, Hixon ML, Finco TC, Perkins ND, Nabel GJ and Baldwin ASJ . (1995). Mol. Cell. Biol., 15, 3450–3459.

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

  • Hingorani R, Bi B, Dao T, Bae Y, Matsuzawa A and Crispe IN . (2000). J. Immunol., 164, 4032–4036.

  • Hobeika AC, Subramaniam PS and Johnson HM . (1997). Oncogene, 14, 1165–1170.

  • Isonishi S, Ohkawa K, Tanaka T and Howell SB . (2000). Br. J. Cancer, 82, 34–38.

  • Jin YH, Yoo KJ, Lee YH and Lee SK . (2000). J. Biol. Chem., 275, 30256–30263.

  • Kardassis D, Papakosta P, Pardali K and Moustakas A . (1999). J. Biol. Chem., 274, 29572–29581.

  • Koutsodontis G, Moustakas A and Kardassis D . (2002). Biochemistry, 41, 12771–12784.

  • Koutsodontis G, Tentes I, Papakosta P, Moustakas A and Kardassis D . (2001). J. Biol. Chem., 276, 29116–29125.

  • LaBaer J, Garrett MD, Stevenson LF and Slingerland JM . (1997). Genes Dev., 11, 847–862.

  • Li JM, Datto MB, Shen X, Hu Y and Wang X . (1998). Nucleic Acid Res., 26, 2449–2456.

  • Livneh E, Shimon T, Bechor E, Doki Y, Schieren I and Weinstein IB . (1996). Oncogene, 12, 1545–1555.

  • Lu S, Jenster G and Epner DE . (2000). Mol. Endocrinol., 14, 753–760.

  • Lu Z, Liu D, Hornia A, Devonish W, Pagano M and Foster DA . (1998). Mol. Cell. Biol., 18, 839–845.

  • Macleod K, Sherry N, Hannon G, Beach D, Tokino T, Kinzler K, Vogelstein B and Jacks T . (1995). Genes Dev., 9, 935–944.

  • Mellor H and Parker PJ . (1998). Biochem. J., 332, 281–292.

  • Mor-Vaknin N, Torgeman A, Galron D, Lochelt M, Flugel RM and Aboud M . (1997). Virology, 232, 337–344.

  • Moustakas A and Kardassis D . (1998). Proc. Natl. Acad. Sci. USA, 95, 6733–6738.

  • Namaba H, Hara T, Tukazaki T, Migita K, Ishikawa N, Ito K, Nagataki S and Yamashita S . (1995). Cancer Res., 55, 2075–3080.

  • Niculescu AB, Chen RX, Smeets M, Hengst L, Prives C and Reed SI . (1998). Mol. Cell. Biol., 18, 629–643.

  • Owen GI, Richer JK, Tung L, Takimoto G and Horwitz KB . (1998). J. Biol. Chem., 273, 10696–10701.

  • Pardali K, Kurisaki A, Moren A, ten Dijke P, Kardassis D and Moustakas A . (2000). J. Biol. Chem., 275, 29244–29256.

  • Revazova T, Dombrovsky A, Lochelt M, Flugel RM and Aboud M . (1995). Cell Mol. Biol. Res., 41, 377–385.

  • Ron D and Kazanietz MG . (1999). FASEB J., 13, 1658–1676.

  • Torgeman A, Ben-Aroya Z, Grunspan A, Zelin E, Butovsky E, Hallak M, Lochelt M, Flugel RM, Livneh E, Wolfson M, Kedar I and Mordechai Aboud M . (2001a). Exp. Cell Res., 271, 169–179.

  • Torgeman A, Mor-Vaknin N and Aboud M . (1999). Virology, 254, 279–287.

  • Torgeman A, Mor-Vaknin N, Zelin E, Ben-Aroya Z, Lochelt M, Flugel RM and Aboud M . (2001b). Virology, 281, 10–20.

  • Toullec D, Pianetti P, Coste H, Bellevergue P, Grand-Perret T, Ajakane M, Baudet V, Boissin P, Boursier E and Loriolle F . (1991). J. Biol. Chem., 266, 15771–15781.

  • Waga S, Hannon GJ, Beach D and Stillman B . (1994). Nature (Lond.), 369, 574–578.

  • Warbrick E . (2000). Bioessays, 22, 997–1006.

  • Yang S . (2003). Trends Genet., 19, 9–12.

  • Zeng YX, Somasundaram K and El-Diery WS . (1997). Nat. Genet., 15, 78–82.

  • Zezula J, Sexl V, Hutter C, Karel A, Schutz W and Freissmut M . (1997). J. Biol. Chem., 272, 29967–29974.

  • Zhang Y, Fujita N and Tsuruo T . (1999). Oncogene, 18, 1131–1138.

  • Zhang H, Hannon G and Beach D . (1994). Genes Dev., 8, 1750–1758.

  • Zhang H, Xiong Y and Beach D . (1993). Mol. Biol. Cell., 4, 897–906.

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Acknowledgements

This study was supported by grants from the Association of International Cancer Research, (AICR), the Israeli Ministry of Science, Culture and Sports (MOS)-German Cancer Research Center (DKFZ), German–Israeli Cooperation in Cancer Research Program, the Israel Science Foundation of The Israeli National Academy of Sciences and Humanities, the Israeli Cancer Association, the Israel Cancer Research Fund (ICRF) and the Chief Scientist Office of the Israeli Health Ministry.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Cancer Research Center, Faculty of Health Sciences,

    Yana Schavinsky-Khrapunsky, Mordechai Aboud & Amram Torgeman

  2. Institute for Applied Biosciences, Ben Gurion University of the Negev, Beer Sheva, 84105, Israel

    Mahmoud Huleihel

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  1. Yana Schavinsky-Khrapunsky
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  2. Mahmoud Huleihel
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  3. Mordechai Aboud
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Correspondence to Mordechai Aboud.

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Schavinsky-Khrapunsky, Y., Huleihel, M., Aboud, M. et al. Role of protein kinase C and the Sp1-p53 complex in activation of p21WAF-1 expression by 12-O-tetradecanoylphorbol-13-acetate in human T cells. Oncogene 22, 5315–5324 (2003). https://doi.org/10.1038/sj.onc.1206782

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