The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
USP44 regulates centrosome positioning to prevent aneuploidy and suppress tumorigenesis
Open accessAbstract
Most human tumors have abnormal numbers of chromosomes, a condition known as aneuploidy. The mitotic checkpoint is an important mechanism that prevents aneuploidy by restraining the activity of the anaphase-promoting complex (APC). The deubiquitinase USP44 was identified as a key regulator of APC activation; however, the physiological importance of USP44 and its impact on cancer biology are unknown. To clarify the role of USP44 in mitosis, we engineered a mouse lacking Usp44. We found that USP44 regulated the mitotic checkpoint and prevented chromosome lagging. Mice lacking Usp44 were prone to the development of spontaneous tumors, particularly in the lungs. Additionally, USP44 was frequently downregulated in human lung cancer, and low expression correlated with a poor prognosis. USP44 inhibited chromosome segregation errors independent of its role in the mitotic checkpoint by regulating centrosome separation, positioning, and mitotic spindle geometry. These functions required direct binding to the centriole protein centrin. Our data reveal a new role for the ubiquitin system in mitotic spindle regulation and underscore the importance of USP44 in the pathogenesis of human cancer.
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Cites
The spindle-assembly checkpoint in space and time
Musacchio, A., & Salmon, E. D. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2163 · Cited by 2,227
The anaphase promoting complex/cyclosome: a machine designed to destroy
Peters, J.-M. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1988 · Cited by 1,315
Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis
Holland, A. J., & Cleveland, D. W. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2718 · Cited by 859
BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice
Baker, D. J., Jeganathan, K. B., Cameron, J. D., Thompson, M., Juneja, S., Kopecka, A., Kumar, R., Jenkins, R. B., de Groen, P. C., Roche, P., et al. (2004) · Nature Genetics · doi:10.1038/ng1382 · Cited by 731
Sensing centromere tension: Aurora B and the regulation of kinetochore function
Lampson, M. A., & Cheeseman, I. M. (2011) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.10.007 · Cited by 375
Cited by
Deubiquitylases From Genes to Organism
Clague, M. J., Barsukov, I., Coulson, J. M., Liu, H., Rigden, D. J., & Urbé, S. (2013) · Physiological Reviews · doi:10.1152/physrev.00002.2013 · Cited by 425
USP7 protects genomic stability by regulating Bub3.
Giovinazzi, S., Sirleto, P., Aksenova, V., Morozov, V. M., Zori, R., Reinhold, W. C., & Ishov, A. M. (2014) · Oncotarget · doi:10.18632/oncotarget.1989 · Cited by 34
Metadata
- Authors
- Zhang, Y., Foreman, O., Wigle, D. A., Kosari, F., Vasmatzis, G., Salisbury, J. L., van Deursen, J., & Galardy, P. J.
- Venue
- Journal of Clinical Investigation
- Published
- 2012-11-26
- Volume
- 122
- Issue
- 12
- Pages
- 4362-4374
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2072974730
- Cited by
- 168
- References
- 5
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhang, Y., Foreman, O., Wigle, D. A., Kosari, F., Vasmatzis, G., Salisbury, J. L., van Deursen, J., & Galardy, P. J. (2012). USP44 regulates centrosome positioning to prevent aneuploidy and suppress tumorigenesis. Journal of Clinical Investigation. https://doi.org/10.1172/jci63084
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