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Overexpression and poly-ubiquitylation of the DEAD-box RNA helicase p68 in colorectal tumours

Abstract

The DEAD box RNA helicase, p68, is upregulated in exponentially growing cells and shows cell cycle-dependent changes in nuclear localization. Although some other DEAD box proteins have been implicated in cancer, there have been no reports of any link between p68 status and carcinogenesis. In the present study we have analysed specimens from 50 patients with colorectal adenocarcinomas, including cases in which an adenomatous polyp was also present, by immunohistochemistry and Western blotting. Our data indicate that p68 protein is consistently overexpressed in tumours as compared with matched normal tissue. Examination of the levels of p68 mRNA from both normal and tumour tissue showed no obvious specific increase in p68 mRNA levels in tumours nor any evidence of underlying mutations in the p68 coding region. Interestingly, however, the accumulated p68 appears to be poly-ubiquitylated, suggesting a possible defect in proteasome-mediated degradation in these tumours. This overexpression/ubiquitylation is observed in both pre-invasive and invasive lesions suggesting that the dysregulation of p68 expression occurs early during tumour development. Finally, we demonstrate that ubiquitylation of p68 occurs in cultured cells, thereby providing a model for the molecular analysis of this process and its potential role in tumorigenesis.

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References

  • Akao Y, Marukawa O, Morikawa H, Nakao K, Kamei M, Hachiya T, Tsujimoto Y . 1995 Cancer Res. 55: 3444–3449

  • Ciechanover A . 1998 EMBO J. 17: 7151–7160

  • Ciechanover A, Orian A, Schwartz AL . 2000 Bioessays 22: 442–451

  • Cummings CJ, Mancini MA, Antalffy B, DeFranco DB, Orr HT, Zoghbi HY . 1998 Nat. Genet. 19: 148–154

  • Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, Scherzinger E, Wanker EE, Mangiarini L, Bates GP . 1997 Cell 90: 537–548

  • Desterro JM, Rodriguez MS, Hay RT . 2000 Cell. Mol. Life Sci. 57: 1207–1219

  • Evan GI, Lewis GK, Ramsay G, Bishop JM . 1985 Mol. Cell. Biol. 5: 3610–3616

  • Fearon ER, Vogelstein B . 1990 Cell 61: 759–767

  • Ford MJ, Anton IA, Lane DP . 1988 Nature 332: 736–738

  • Fuller-Pace FV . 1994 Trends Cell. Biol. 4: 271–274

  • Gavioli R, Frisan T, Vertuani S, Bornkamm GW, Masucci MG . 2001 Nature Cell Biol. 3: 283–288

  • George RE, Kenyon RM, McGuckin AG, Malcolm AJ, Pearson AD, Lunec J . 1996 Oncogene 12: 1583–1587

  • Godbout R, Squire J . 1993 Proc. Natl. Acad. Sci. USA 90: 7578–7582

  • Gregory MA, Hann SR . 2000 Mol. Cell. Biol. 20: 2423–2435

  • Harlow E, Lane D . 1988 Antibodies: A laboratory Manual Cold Spring Harbor Laboratory, New York

  • Hirling H, Scheffner M, Restle T, Stahl H . 1989 Nature 339: 562–564

  • Hochstrasser M . 1996 Cell 84: 813–815

  • Iggo RD, Jamieson DJ, MacNeill SA, Southgate J, McPheat J, Lane DP . 1991 Mol. Cell. Biol. 11: 1326–1333

  • Iggo RD, Lane DP . 1989 EMBO J. 8: 1827–1831

  • Kopito RR, Sitia R . 2000 EMBO Rep. 1: 225–231

  • Lane DP, Hoeffler WK . 1980 Nature 288: 167–170

  • Mahajan R, Delphin C, Guan T, Gerace L, Melchior F . 1997 Cell 88: 97–107

  • Matunis MJ, Wu J, Blobel G . 1998 J. Cell. Biol. 140: 499–509

  • Muller S, Matunis MJ, Dejean A . 1998 EMBO J. 17: 61–70

  • Nakagawa Y, Morikawa H, Hirata I, Shiozaki M, Matsumoto A, Maemura K, Nishikawa T, Niki M, Tanigawa N, Ikegami M, Katsu K, Akao Y . 1999 Br. J. Cancer 80: 914–917

  • Nicol SM, Causevic M, Prescott AR, Fuller-Pace FV . 2000 Exp. Cell. Res. 257: 272–280

  • Rodriguez MS, Desterro JM, Lain S, Midgley CA, Lane DP, Hay RT . 1999 EMBO J. 18: 6455–6461

  • Scheffner M, Huibregtse JM, Vierstra RD, Howley PM . 1993 Cell 75: 495–505

  • Spence J, Gali RR, Dittmar G, Sherman F, Karin M, Finley D . 2000 Cell 102: 67–76

  • Squire JA, Thorner PS, Weitzman S, Maggi JD, Dirks P, Doyle J, Hale M, Godbout R . 1995 Oncogene 10: 1417–1422

  • Stevenson RJ, Hamilton SJ, MacCallum DE, Hall PA, Fuller-Pace FV . 1998 J. Pathol. 184: 351–359

  • Treier M, Staszewski LM, Bohmann D . 1994 Cell 78: 787–798

  • Webster GA, Perkins ND . 1999 Mol. Cell. Biol. 19: 3485–3495

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Acknowledgements

We thank Liz Furrie, Ron Hay and David Lane for helpful discussions, George Thomson, Andy Grant and Jim Gibbs for advice on immunohistochemistry/imaging and our colleagues in the GI Laboratory for making available the tissues used in this study. This work was funded by grants from the Medical Research Council (UK), the Association for International Cancer Research and the Chief Scientist's Office of the Scottish Executive Health Department. F Fuller-Pace is a Medical Research Council Senior Fellow.

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Correspondence to Frances V Fuller-Pace.

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Causevic, M., Hislop, R., Kernohan, N. et al. Overexpression and poly-ubiquitylation of the DEAD-box RNA helicase p68 in colorectal tumours. Oncogene 20, 7734–7743 (2001). https://doi.org/10.1038/sj.onc.1204976

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Keywords

  • p68 RNA helicase
  • colorectal cancer
  • overexpression
  • ubiquitylation

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