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A key role of the hSNF5/INI1 tumour suppressor in the control of the G1-S transition of the cell cycle

Oncogene volume 21, pages 6403–6412 (2002)Cite this article

Abstract

The hSNF5/INI1 gene encodes a member of the SWI/SNF chromatin remodelling complexes. It was recently identified as a tumour suppressor gene mutated in sporadic and hereditary Malignant Rhabdoid Tumours (MRT). However, the role of hSNF5/INI1 loss-of-function in tumour development is still unknown. Here, we show that the ectopic expression of wild-type hSNF5/INI1, but not that of truncated versions, leads to a cell cycle arrest by inhibiting the entry into S phase of MRT cells. This G1 arrest is associated with down-regulation of a subset of E2F targets including cyclin A, E2F1 and CDC6. This arrest can be reverted by coexpression of cyclin D1, cyclin E or viral E1A, whereas it cannot be counteracted by pRB-binding deficient E1A mutants. Moreover, hSNF5/INI1 is not able to arrest cells lacking a functional pRB. These observations suggest that the hSNF5/INI1-induced G1 arrest is dependent upon the presence of a functional pRB. However, the observation that a constitutively active pRB can efficiently arrest MRT cells indicates that hSNF5/INI1, at the difference of the ATPase subunits of the SWI/SNF complex, is dispensable for pRB function. Altogether, these data show that hSNF5/INI1 is a potent regulator of the entry into S phase, an effect that may account for its tumour suppressor role.

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References

  • Biegel JA, Fogelgren B, Zhou JY, James CD, Janss AJ, Allen JC, Zagzag D, Raffel C, Rorke LB . 2000 Clin. Cancer Res. 6: 2759–2763

  • Biegel JA, Zhou JY, Rorke LB, Stenstrom C, Wainwright LM, Fogelgren B . 1999 Cancer Res. 59: 74–79

  • Bultman S, Gebuhr T, Yee D, La Mantia C, Nicholson J, Gilliam A, Randazzo F, Metzger D, Chambon P, Crabtree G, Magnuson T . 2000 Mol. Cell 6: 1287–1295

  • Craig C, Kim M, Ohri E, Wersto R, Katayose D, Li Z, Choi YH, Mudahar B, Srivastava S, Seth P, Cowan K . 1998 Oncogene 16: 265–272

  • Craig E, Zhang ZK, Davies KP, Kalpana GV . 2002 EMBO J. 21: 31–42

  • Dauphinot L, De Oliveira C, Melot T, Sevenet N, Thomas V, Weissman BE, Delattre O . 2001 Oncogene 20: 3258–3265

  • DeCristofaro MF, Betz BL, Wang W, Weissman BE . 1999 Oncogene 18: 7559–7565

  • Dunaief JL, Strober BE, Guha S, Khavari PA, Alin K, Luban J, Begemann M, Crabtree GR, Goff SP . 1994 Cell 79: 119–130

  • Gallimore PH, Turnell AS . 2001 Oncogene 20: 7824–7835

  • Guidi CJ, Sands AT, Zambrowicz BP, Turner TK, Demers DA, Webster W, Smith TW, Imbalzano AN, Jones SN . 2001 Mol. Cell. Biol. 21: 3598–3603

  • Hamel PA, Gill RM, Phillips RA, Gallie BL . 1992 Mol. Cell. Biol. 12: 3431–3438

  • Harbour JW, Luo RX, Dei Santi A, Postigo AA, Dean DC . 1999 Cell 98: 859–869

  • Herrera VL, Chobanian AV, Ruiz-Opazo N . 1988 Science 241: 221–223

  • Kalpana GV, Marmon S, Wang W, Crabtree GR, Goff SP . 1994 Science 266: 2002–2006

  • Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, Stockert E, Day III RS, Johnson BE, Skolnick MH . 1994 Science 264: 436–440

  • Kingston RE, Narlikar GJ . 1999 Genes Dev. 13: 2339–2352

  • Klochendler-Yeivin A, Fiette L, Barra J, Muchardt C, Babinet C, Yaniv M . 2000 EMBO Rep. 1: 500–506

  • Klochendler-Yeivin A, Muchardt C, Yaniv M . 2002 Curr. Opin. Genet. Dev. 12: 73–79

  • Lundberg AS, Weinberg RA . 1998 Mol. Cell. Biol. 18: 753–761

  • Muchardt C, Sardet C, Bourachot B, Onufryk C, Yaniv M . 1995 Nucleic Acids Res. 23: 1127–1132

  • Nie Z, Xue Y, Yang D, Zhou S, Deroo BJ, Archer TK, Wang W . 2000 Mol. Cell. Biol. 20: 8879–8888

  • Phelan ML, Sif S, Narlikar GJ, Kingston RE . 1999 Mol. Cell 3: 247–253

  • Remvikos Y, Vielh P, Padoy E, Benyahia B, Voillemot N, Magdelenat H . 1991 Br. J. Cancer 64: 501–507

  • Roberts CW, Galusha SA, McMenamin ME, Fletcher CD, Orkin SH . 2000 Proc. Natl. Acad. Sci. USA 97: 13796–13800

  • Savla J, Chen TT, Schneider NR, Timmons CF, Delattre O, Tomlinson GE . 2000 J. Natl. Cancer Inst. 92: 648–650

  • Sevenet N, Lellouch-Tubiana A, Schofield D, Hoang-Xuan K, Gessler M, Birnbaum D, Jeanpierre C, Jouvet A, Delattre O . 1999a Hum. Mol. Genet. 8: 2359–2368

  • Sevenet N, Sheridan E, Amram D, Schneider P, Handgretinger R, Delattre O . 1999b Am. J. Hum. Genet. 65: 1342–1348

  • Shanahan F, Seghezzi W, Parry D, Mahony D, Lees E . 1999 Mol. Cell. Biol. 19: 1460–1469

  • Shew JY, Lin BT, Chen PL, Tseng BY, Yang-Feng TL, Lee WH . 1990 Proc. Natl. Acad. Sci. USA 87: 6–10

  • Sif S, Stukenberg PT, Kirschner MW, Kingston RE . 1998 Genes Dev. 12: 2842–2851

  • Staehling-Hampton K, Ciampa PJ, Brook A, Dyson N . 1999 Genetics 153: 275–287

  • Strobeck MW, Knudsen KE, Fribourg AF, DeCristofaro MF, Weissman BE, Imbalzano AN, Knudsen ES . 2000 Proc. Natl. Acad. Sci. USA 97: 7748–7753

  • Strobeck MW, Reisman DN, Gunawardena RW, Betz BL, Angus SP, Knudsen KE, Kowalik TF, Weissman BE, Knudsen ES . 2001 J. Biol. Chem. 277: 4782–4789

  • Strober BE, Dunaief JL, Guha, Goff SP . 1996 Mol. Cell. Biol. 16: 1576–1583

  • Sudarsanam P, Winston F . 2000 Trends Genet. 16: 345–351

  • Taylor MD, Gokgoz N, Andrulis IL, Mainprize TG, Drake JM, Rutka JT . 2000 Am. J. Hum. Genet. 66: 1403–1406

  • Trouche D, Kouzarides T . 1996 Proc. Natl. Acad. Sci. USA 93: 1439–1442

  • Trouche D, Le Chalony C, Muchardt C, Yaniv M, Kouzarides T . 1997 Proc. Natl. Acad. Sci. USA 94: 11268–11273

  • Versteege I, Sevenet N, Lange J, Rousseau-Merck MF, Ambros P, Handgretinger R, Aurias A, Delattre O . 1998 Nature 394: 203–206

  • Wang W, Cote J, Xue Y, Zhou S, Khavari PA, Biggar SR, Muchardt C, Kalpana GV, Goff SP, Yaniv M, Workman JL, Crabtree GR . 1996 EMBO J. 15: 5370–5382

  • Wong AK, Shanahan F, Chen Y, Lian L, Ha P, Hendricks K, Ghaffari S, Iliev D, Penn B, Woodland AM, Smith R, Salada G, Carillo A, Laity K, Gupte J, Swedlund B, Tavtigian SV, Teng DH, Lees E . 2000 Cancer Res. 60: 6171–6177

  • Xiao ZX, Chen J, Levine AJ, Modjtahedi N, Xing J, Sellers WR, Livingston DM . 1995 Nature 375: 694–698

  • Zhang HS, Gavin M, Dahiya A, Postigo AA, Ma D, Luo RX, Harbour HW, Dean DC . 2000 Cell 101: 79–89

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Acknowledgements

We thank Christian Muchardt, Christian Larsen, Didier Trouche, Annick Harel-Bellan and Pierre Savatier for providing materials used in this study. I Versteege is a recipient of a fellowship from La Fondation pour la Recherche Médicale. S Medjkane is a recipient of a fellowship from the Ministère de la Recherche et de la Technologie. This work was supported in part by grants from the Association pour la Recherche contre le Cancer, the European Community Marie Curie fellowship and the Comité de Paris of the Ligue Nationale Contre le Cancer.

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Author notes

  1. Isabella Versteege and Souhila Medjkane: These two authors contributed equally to this work

Authors and Affiliations

  1. INSERM U509, Laboratoire de Pathologie Moléculaire des Cancers, Institut Curie, 26 rue d'Ulm, Paris, 75248, Cedex 05, France

    Isabella Versteege, Souhila Medjkane & Olivier Delattre

  2. UMR 147, Institut Curie, 26 rue d'Ulm, Paris, 75248, Cedex 05, France

    Danny Rouillard

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  1. Isabella Versteege
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  2. Souhila Medjkane
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  4. Olivier Delattre
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Correspondence to Olivier Delattre.

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Versteege, I., Medjkane, S., Rouillard, D. et al. A key role of the hSNF5/INI1 tumour suppressor in the control of the G1-S transition of the cell cycle. Oncogene 21, 6403–6412 (2002). https://doi.org/10.1038/sj.onc.1205841

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