NuMA is required for the proper completion of mitosis - PubMed (original) (raw)
NuMA is required for the proper completion of mitosis
D A Compton et al. J Cell Biol. 1993 Feb.
Abstract
NuMA is a 236-kD intranuclear protein that during mitosis is distributed into each daughter cell by association with the pericentrosomal domain of the spindle apparatus. The NuMA polypeptide consists of globular head and tail domains separated by a discontinuous 1500 amino acid coiled-coil spacer. Expression of human NuMA lacking its globular head domain results in cells that fail to undergo cytokinesis and assemble multiple small nuclei (micronuclei) in the subsequent interphase despite the appropriate localization of the truncated NuMA to both the nucleus and spindle poles. This dominant phenotype is morphologically identical to that of the tsBN2 cell line that carries a temperature-sensitive mutation in the chromatin-binding protein RCC1. At the restrictive temperature, these cells end mitosis without completing cytokinesis followed by micronucleation in the subsequent interphase. We demonstrate that the wild-type NuMA is degraded in the latest mitotic stages in these mutant cells and that NuMA is excluded from the micronuclei that assemble post-mitotically. Elevation of NuMA levels in these mutant cells by forcing the expression of wild-type NuMA is sufficient to restore post-mitotic assembly of a single normal-sized nucleus. Expression of human NuMA lacking its globular tail domain results in NuMA that fails both to target to interphase nuclei and to bind to the mitotic spindle. In the presence of this mutant, cells transit through mitosis normally, but assemble micronuclei in each daughter cell. The sum of these findings demonstrate that NuMA function is required during mitosis for the terminal phases of chromosome separation and/or nuclear reassembly.
Similar articles
- Mutation of the predicted p34cdc2 phosphorylation sites in NuMA impair the assembly of the mitotic spindle and block mitosis.
Compton DA, Luo C. Compton DA, et al. J Cell Sci. 1995 Feb;108 ( Pt 2):621-33. doi: 10.1242/jcs.108.2.621. J Cell Sci. 1995. PMID: 7769006 - A nonerythroid isoform of protein 4.1R interacts with the nuclear mitotic apparatus (NuMA) protein.
Mattagajasingh SN, Huang SC, Hartenstein JS, Snyder M, Marchesi VT, Benz EJ. Mattagajasingh SN, et al. J Cell Biol. 1999 Apr 5;145(1):29-43. doi: 10.1083/jcb.145.1.29. J Cell Biol. 1999. PMID: 10189366 Free PMC article. - NuMA: a bipartite nuclear location signal and other functional properties of the tail domain.
Gueth-Hallonet C, Weber K, Osborn M. Gueth-Hallonet C, et al. Exp Cell Res. 1996 May 25;225(1):207-18. doi: 10.1006/excr.1996.0171. Exp Cell Res. 1996. PMID: 8635513 - Does NuMA have a scaffold function in the interphase nucleus?
Harborth J, Osborn M. Harborth J, et al. Crit Rev Eukaryot Gene Expr. 1999;9(3-4):319-28. doi: 10.1615/critreveukargeneexpr.v9.i3-4.160. Crit Rev Eukaryot Gene Expr. 1999. PMID: 10651248 Review. - NuMA, a nuclear protein involved in mitosis and nuclear reformation.
Compton DA, Cleveland DW. Compton DA, et al. Curr Opin Cell Biol. 1994 Jun;6(3):343-6. doi: 10.1016/0955-0674(94)90024-8. Curr Opin Cell Biol. 1994. PMID: 7917323 Review.
Cited by
- NuMA after 30 years: the matrix revisited.
Radulescu AE, Cleveland DW. Radulescu AE, et al. Trends Cell Biol. 2010 Apr;20(4):214-22. doi: 10.1016/j.tcb.2010.01.003. Trends Cell Biol. 2010. PMID: 20137953 Free PMC article. Review. - Downregulated Trophinin-Associated Protein Plays a Critical Role in Human Hepatocellular Carcinoma Through Upregulation of Tumor Cell Growth and Migration.
Lian Y, Fan W, Huang Y, Wang H, Wang J, Zhou L, Wu X, Deng M, Huang Y. Lian Y, et al. Oncol Res. 2018 Jun 11;26(5):691-701. doi: 10.3727/096504017X15101398724809. Epub 2017 Nov 8. Oncol Res. 2018. PMID: 29117881 Free PMC article. - NuMA is required for the selective induction of p53 target genes.
Ohata H, Miyazaki M, Otomo R, Matsushima-Hibiya Y, Otsubo C, Nagase T, Arakawa H, Yokota J, Nakagama H, Taya Y, Enari M. Ohata H, et al. Mol Cell Biol. 2013 Jun;33(12):2447-57. doi: 10.1128/MCB.01221-12. Epub 2013 Apr 15. Mol Cell Biol. 2013. PMID: 23589328 Free PMC article. - [Noninvasive and invasive bladder cancer: diagnostics and treatment].
Goebell PJ, Vom Dorp F, Rödel C, Frohneberg D, Thüroff JW, Jocham D, Stief C, Roth S, Knüchel R, Schmidt KW, Kausch I, Zaak D, Wiesner C, Miller K, Sauer R, Rübben H. Goebell PJ, et al. Urologe A. 2006 Jul;45(7):873-84; quiz 885. doi: 10.1007/s00120-006-1065-z. Urologe A. 2006. PMID: 16791629 Review. German. - Epitope mapping and direct visualization of the parallel, in-register arrangement of the double-stranded coiled-coil in the NuMA protein.
Harborth J, Weber K, Osborn M. Harborth J, et al. EMBO J. 1995 Jun 1;14(11):2447-60. doi: 10.1002/j.1460-2075.1995.tb07242.x. EMBO J. 1995. PMID: 7781599 Free PMC article.
References
- Nature. 1970 Aug 15;227(5259):680-5 - PubMed
- Mol Biol Cell. 1992 Nov;3(11):1259-67 - PubMed
- J Cell Biol. 1977 Jun;73(3):616-37 - PubMed
- Cell. 1978 Oct;15(2):475-83 - PubMed
- J Cell Biol. 1978 Nov;79(2 Pt 1):546-66 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous