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Publication : Mitotic chromosome condensation mediated by the retinoblastoma protein is tumor-suppressive.

First Author  Coschi CH Year  2010
Journal  Genes Dev Volume  24
Issue  13 Pages  1351-63
PubMed ID  20551166 Mgi Jnum  J:161363
Mgi Id  MGI:4458946 Doi  10.1101/gad.1917610
Citation  Coschi CH, et al. (2010) Mitotic chromosome condensation mediated by the retinoblastoma protein is tumor-suppressive. Genes Dev 24(13):1351-63
abstractText  Condensation and segregation of mitotic chromosomes is a critical process for cellular propagation, and, in mammals, mitotic errors can contribute to the pathogenesis of cancer. In this report, we demonstrate that the retinoblastoma protein (pRB), a well-known regulator of progression through the G1 phase of the cell cycle, plays a critical role in mitotic chromosome condensation that is independent of G1-to-S-phase regulation. Using gene targeted mutant mice, we studied this aspect of pRB function in isolation, and demonstrate that it is an essential part of pRB-mediated tumor suppression. Cancer-prone Trp53(-/-) mice succumb to more aggressive forms of cancer when pRB's ability to condense chromosomes is compromised. Furthermore, we demonstrate that defective mitotic chromosome structure caused by mutant pRB accelerates loss of heterozygosity, leading to earlier tumor formation in Trp53(+/-) mice. These data reveal a new mechanism of tumor suppression, facilitated by pRB, in which genome stability is maintained by proper condensation of mitotic chromosomes.
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