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  • Original Paper
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Role of pescadillo in the transformation and immortalization of mammalian cells

Abstract

The murine and human homologs of the zebrafish pescadillo protein (Pes1 and PES1, respectively) play important roles in ribosome biogenesis and DNA replication. We investigated the effect of Pes1 on the growth of mouse embryo (3T3-like) fibroblasts and conditionally immortalized human fibroblasts expressing the SV40 T antigen (AR5 cells). Increased expression of Pes1 causes transformation of mouse and human fibroblasts in culture (colony formation in soft agar). Although Pes1 can replace the SV40 T antigen in inducing colony formation in soft agar, it cannot substitute the T antigen in the immortalization of human fibroblasts, indicating that it distinguishes between the two functions. As the biological effects of Pes1 are similar to those of the insulin receptor substrate-1 (IRS-1), we investigated the interactions of Pes1 with IRS-1 itself and with the SV40 T antigen. The Pes1 protein (which localizes to the nuclei and nucleoli of cells) interacts with both IRS-1 and the SV40 T antigen, and markedly decreases the interaction of T antigen with p53. Taken together, these results suggest mechanisms for the ability of Pes1 to transform cells, and its failure to immortalize them.

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References

  • Ali SH and DeCaprio JA . (2001). Sem. Cancer Biol., 11, 15–22.

  • Allende ML, Amsterdam A, Becker T, Kawakami K, Gaiano N and Hopkins N . (1996). Genes Dev., 10, 3141–3155.

  • Baserga R . (1984). Exp. Cell Res., 151, 1–5.

  • Bohni R, Riesco-Escovar J, Oldham S, Brogiolo W, Stocker H, Andruss BF, Beckingham K and Hafen E . (1999). Cell, 97, 865–875.

  • Chang LS, Pan S, Pater MM and Di Mayorca G . (1985). Virology, 146, 246–261.

  • Chang Q, Li Y, White MF, Fletcher JA and Xiao S . (2002). Cancer Res., 62, 6035–6038.

  • Comai L, Song Y, Tan C and Bui T . (2000). Cell Growth Differ., 11, 63–70.

  • Cristofalo V, Phillips PD, Sorger T and Gerhard G . (1989). J. Gerontol., 44, 55–62.

  • D'Ambrosio C, Keller SR, Morrione A, Lienhard GE, Baserga R and Surmacz E . (1995). Cell Growth Differ., 6, 557–562.

  • Du YCN and Stillman B . (2002). Cell, 109, 835–884.

  • Fanning E . (1992). J. Virol., 66, 1289–1293.

  • Fraser RSS and Nurse P . (1978). Nature, 27, 726–730.

  • Grummt I . (1999). Progr. Nucl. Acid Res. Mol. Biol., 62, 109–153.

  • Grummt I . (2003). Genes Dev., 17, 1691–1702.

  • Haque J, Boger S, Li J and Duncan SA . (2000). Genomics, 70, 201–210.

  • Hartwell LH . (1978). J. Cell Biol., 77, 627–637.

  • Jorgensen P, Nishikawa JL, Breitkreutz BJ and Tyers M . (2002). Science, 297, 395–400.

  • Kinoshita Y, Jarell AD, Flaman JM, Foltz G, Schuster J, Sopher BL, Irvi DK, Kornblum HI, Nelson PS, Hoieter P and Morrison RS . (2001). J. Biol. Chem., 276, 6656–6665.

  • Lassak A, Delvalle L, Peruzzi F, Wang JY, Enam S, Croul S, Khalili K and Reiss K . (2002). J. Biol. Chem., 277, 17231–17238.

  • Lerch-Gaggl A, Haque J, Li J, Ning G, Traktman P and Duncan SA . (2002). J. Biol. Chem., 277, 45347–45355.

  • Liu J-P, Baker J, Perkins AS, Robertson EJ and Efstratiadis A . (1993). Cell, 75, 59–72.

  • Manfredi JJ and Prives C . (1994). Biochim. Biophys. Acta, 1198, 65–83.

  • Manke IA, Lowery DM, Nguyen A and Yaffe MB . (2003). Science, 302, 636–639.

  • Montagne J, Stewar MJ, Stocker H, Hafen E, Kozma SC and Thomas G . (1999). Science, 285, 2126–2129.

  • Moss T and Stefanovsky VY . (1995). Progr. Nucleic Acid Res. Mol. Biol., 50, 25–66.

  • Neufeld DS, Ripley S, Henderson A and Ozer HL . (1987). Mol. Cell. Biol., 7, 2794–2802.

  • O'Brien T and Tjian R . (2000). Proc. Natl. Acad. Sci. USA, 97, 2456–2461.

  • Oeffinger M, Lueng A, Lamond A and Tollervey D . (2002). RNA, 8, 626–636.

  • Peruzzi F, Prisco M, Dews M, Salomoni P, Grassilli E, Romano G, Calabrett B and Baserga R . (1999). Mol. Cell. Biol., 19, 7203–7215.

  • Pete G, Fuller GR, Oldham JM, Smith DR, D'Ercole AJ, Kahn CR and Lund PK . (1999). Endocrinology, 140, 5478–5487.

  • Pipas JM and Levine AJ . (2001). Sem. Cancer Biol., 11, 23–30.

  • Prisco M, Hongo A, Rizzo MG, Sacchi A and Baserga R . (1997). Mol. Cell. Biol., 17, 1084–1092.

  • Prisco M, Maiorana A, Guerzoni C, Calin G, Calabretta B, Voit R, Grummt I and Baserga R . (2004). Mol. Cell. Biol, 24, 5421–5433.

  • Prisco M, Santini F, Baffa R, Liu M, Drakas R, Wu A and Baserga R . (2002). J. Biol. Chem., 277, 32078–32085.

  • Radna RL, Caton Y, Jha KK, Kaplan P, Li G, Traganos F and Ozer HL . (1989). Mol. Cell. Biol., 9, 3093–3096.

  • Reeder RH . (1999). Progr. Nucleic Acid Res. Mol. Biol., 62, 293–327.

  • Reiss K, Valentinis B, Tu X, Xu SQ and Baserga R . (1998). Exp. Cell Res., 242, 361–372.

  • Resnick-Silverman L, Pang Z, Li G, Jha KK and Ozer HL . (1991). J. Virol., 65, 2845–2852.

  • Rubini M, Hongo A, D'Ambrosio C and Baserga R . (1997). Exp. Cell Res., 230, 284–292.

  • Sell C, Dumenil G, Deveaud C, Miura M, Coppola D, DeAngelis T, Rubin R, Efstratiadis A and Baserga R . (1994). Mol. Cell. Biol., 14, 3604–3612.

  • Sell C, Rubini M, Rubin R, Liu J-P, Efstratiadis A and Baserga R . (1993). Proc. Natl. Acad. Sci. USA, 90, 11217–11221.

  • Shima H, Pende M, Chen Y, Fumagalli S, Thomas G and Kozma SC . (1998). EMBO J., 17, 6649–6659.

  • Soprano KJ, Dev VG, Croce C and Baserga R . (1979). Proc. Natl. Acad. Sci. USA, 76, 3885–3889.

  • Soprano KJ, Galanti N, Jonak G J, McKercher S, Pipas JM, Peden KWC and Baserga R . (1983). Mol. Cell. Biol., 3, 214–219.

  • Sun H, Tu X, Prisco M, Wu A, Casiburi I and Baserga R . (2003). Mol. Endocrinol., 17, 472–486.

  • Talavera A and Basilico C . (1977). J. Cell. Physiol., 92, 425–436.

  • Tu X, Batta P, Innocent N, Prisco M, Casaburi I, Belletti B and Baserga R . (2002). J. Biol. Chem., 277, 44357–44365.

  • Valentinis B, Navarro M, Zanocco-Marani T, Edmonds P, McCormick J, Morrione A, Sacchi A, Romano G, Reiss K and Baserga R . (2000). J. Biol. Chem., 275, 25451–25459.

  • Verdu J, Buratovich MA, Wilder EL and Birnbaum MJ . (1999). Nat. Cell Biol., 1, 500–506.

  • Voit R, Kuhn A, Sander EE and Grummt I . (1995). Nucleic Acids Res., 23, 2593–2599.

  • Voit R, Schnapp A, Kuhn A, Rosenbauer H, Hirschmann P, Stunnenberg HG and Grummt I . (1992). EMBO J., 11, 221–2218.

  • White JA, Carter SG, Ozer HL and Boyd AL . (1992). Exp. Cell Res., 203, 157–163.

  • White MF . (1998). Mol. Cell. Biochem., 182, 3–11.

  • Yu X, Silva Chin CC, He M, Mer G and Chen J . (2003). Science, 302, 639–642.

  • Zhai W, Tuan J and Comai L . (1997). Genes Dev., 11, 1605–1617.

  • Zhou-Li F, D'Ambrosio C, Li S, Surmacz E and Baserga R . (1995). Mol. Cell Biol., 15, 4232–4239.

  • Zhou-Li F, Xu SG, Dews M and Baserga R . (1997). Oncogene, 15, 961–970.

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Acknowledgements

This work was supported by grants AG16291 and CA89640 from the National Institutes of Health.

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Correspondence to Renato Baserga.

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Maiorana, A., Tu, X., Cheng, G. et al. Role of pescadillo in the transformation and immortalization of mammalian cells. Oncogene 23, 7116–7124 (2004). https://doi.org/10.1038/sj.onc.1207916

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