Tetraploid State Induces p53-dependent Arrest of Nontransformed Mammalian Cells in G1

Molecular Biology of the Cell - Tập 12 Số 5 - Trang 1315-1328 - 2001
Paul R. Andreassen1, Olivier Lohez1, Françoise Lacroix1, Robert L. Margolis1
1Institut de Biologie Structurale Jean-Pierre Ebel (Commissariatà l'Energie Atomique-Centre National de la Recherche Scientifique), 38027 Grenoble Cedex 1, France

Tóm tắt

A “spindle assembly” checkpoint has been described that arrests cells in G1 following inappropriate exit from mitosis in the presence of microtubule inhibitors. We have here addressed the question of whether the resulting tetraploid state itself, rather than failure of spindle function or induction of spindle damage, acts as a checkpoint to arrest cells in G1. Dihydrocytochalasin B induces cleavage failure in cells where spindle function and chromatid segregation are both normal. Notably, we show here that nontransformed REF-52 cells arrest indefinitely in tetraploid G1 following cleavage failure. The spindle assembly checkpoint and the tetraploidization checkpoint that we describe here are likely to be equivalent. Both involve arrest in G1 with inactive cdk2 kinase, hypophosphorylated retinoblastoma protein, and elevated levels of p21WAF1 and cyclin E. Furthermore, both require p53. We show that failure to arrest in G1 following tetraploidization rapidly results in aneuploidy. Similar tetraploid G1 arrest results have been obtained with mouse NIH3T3 and human IMR-90 cells. Thus, we propose that a general checkpoint control acts in G1 to recognize tetraploid cells and induce their arrest and thereby prevents the propagation of errors of late mitosis and the generation of aneuploidy. As such, the tetraploidy checkpoint may be a critical activity of p53 in its role of ensuring genomic integrity.

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Tài liệu tham khảo

Andreassen P.R., 1994, J. Cell Biol., 127, 789, 10.1083/jcb.127.3.789

Andreassen P.R., 1996, Mutat. Res., 372, 181, 10.1016/S0027-5107(96)00138-8

Aubin J.E., 1981, Exp. Cell Res., 136, 63, 10.1016/0014-4827(81)90038-0

Baker S.J., 1990, Science, 249, 912, 10.1126/science.2144057

Banin S., 1998, Science, 281, 1674, 10.1126/science.281.5383.1674

Brénot-Bosc F., 1995, Chromosoma, 103, 517, 10.1007/BF00355316

Buchkovich K., 1989, Cell, 58, 1097, 10.1016/0092-8674(89)90508-4

Cahill D.P., 1998, Nature, 392, 300, 10.1038/32688

Canman C.E., 1998, Science, 281, 1677, 10.1126/science.281.5383.1677

Chan G.K., 1999, J. Cell Biol., 146, 941, 10.1083/jcb.146.5.941

Chen P.L., 1989, Cell, 58, 1193, 10.1016/0092-8674(89)90517-5

Cox L.S., 1995, Bioessays, 17, 501, 10.1002/bies.950170606

Cross S.M., 1995, Science, 267, 1353, 10.1126/science.7871434

Davis F.M., 1983, Proc. Natl. Acad. Sci. USA, 80, 2926, 10.1073/pnas.80.10.2926

Di Leonardo A., 1997, Cancer Res., 57, 1013

Donehower L.A., 1995, Genes Dev., 9, 882, 10.1101/gad.9.7.882

Donehower L.A., 1992, Nature, 356, 215, 10.1038/356215a0

Duesberg P., 1998, Proc. Natl. Acad. Sci. USA, 95, 13692, 10.1073/pnas.95.23.13692

Dulic V., 1994, Cell, 76, 1013, 10.1016/0092-8674(94)90379-4

Dynlacht B.D., 1994, Genes Dev., 8, 1772, 10.1101/gad.8.15.1772

El-Deiry W.S., 1993, Cell, 75, 817, 10.1016/0092-8674(93)90500-P

Galipeau P.C., 1996, Proc. Natl. Acad. Sci. USA, 93, 7081, 10.1073/pnas.93.14.7081

Galitski T., 1999, Science, 285, 251, 10.1126/science.285.5425.251

Gorbsky G.J., 1998, J. Cell Biol., 141, 1193, 10.1083/jcb.141.5.1193

Gottlieb E., 1994, EMBO J., 13, 1368, 10.1002/j.1460-2075.1994.tb06390.x

Hartwell L., 1992, Cell, 71, 543, 10.1016/0092-8674(92)90586-2

Harvey M., 1993, Oncogene, 8, 2457

Hinchcliffe E.H., 2001, Science, 291, 1547, 10.1126/science.1056866

Kastan M.B., 1992, Cell, 71, 587, 10.1016/0092-8674(92)90593-2

Kato J., 1993, Genes Dev., 7, 331, 10.1101/gad.7.3.331

Koff A., 1992, Science, 257, 1689, 10.1126/science.1388288

Kung A.L., 1990, Proc. Natl. Acad. Sci. USA, 87, 9553, 10.1073/pnas.87.24.9553

Lanni J.S., 1998, Mol. Cell. Biol., 18, 1055, 10.1128/MCB.18.2.1055

Lengauer C., 1998, Nature, 396, 643, 10.1038/25292

Li R., 1997, Proc. Natl. Acad. Sci. USA, 94, 14506, 10.1073/pnas.94.26.14506

Lowe S.W., 1993, Cell, 74, 957, 10.1016/0092-8674(93)90719-7

Martineau S.N., 1995, J. Cell Biol., 131, 191, 10.1083/jcb.131.1.191

Minn A.J., 1996, Genes Dev., 10, 2621, 10.1101/gad.10.20.2621

Ornitz D.M., 1987, Science, 238, 188, 10.1126/science.2821617

Pagano M., 1993, J. Cell Biol., 121, 101, 10.1083/jcb.121.1.101

Perry M.E., 1992, Proc. Natl. Acad. Sci. USA, 89, 8112, 10.1073/pnas.89.17.8112

Rabinovitch P.S., 1989, Lab. Invest., 60, 65

Sandberg A.A., 1977, Cancer Res., 37, 2950

Schimke R.T., 1991, Cold Spring Harbor Symp. Quant. Biol., 56, 417, 10.1101/SQB.1991.056.01.049

Shackney S.E., 1989, Cancer Res., 49, 3344

Shaulian E., 1992, Mol. Cell. Biol., 12, 5581, 10.1128/MCB.12.12.5581

Stewart Z.A., 1999, Mol. Cell. Biol., 19, 205, 10.1128/MCB.19.1.205

Taylor S.S., 1997, Cell, 89, 727, 10.1016/S0092-8674(00)80255-X

Trielli M.O., 1996, J. Cell Biol., 135, 689, 10.1083/jcb.135.3.689

Tsai L.-H., 1993, Oncogene, 8, 1593

Weintraub S.J., 1992, Nature, 358, 259, 10.1038/358259a0

Yonish-Rouach E., 1991, Nature, 352, 345, 10.1038/352345a0

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Molecular Biology of the Cell

Tập 12 Số 5

1315-1328

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