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p21/Cyclin E pathway modulates anticlastogenic function of Bmi-1 in cancer cells.
- Source :
- International Journal of Cancer; Mar2015, Vol. 136 Issue 6, p1361-1370, 10p
- Publication Year :
- 2015
-
Abstract
- Apart from regulating stem cell self-renewal, embryonic development and proliferation, Bmi-1 has been recently reported to be critical in the maintenance of genome integrity. In searching for novel mechanisms underlying the anticlastogenic function of Bmi-1, we observed, for the first time, that Bmi-1 positively regulates p21 expression. We extended the finding that Bmi-1 deficiency induced chromosome breaks in multiple cancer cell models. Interestingly, we further demonstrated that knockdown of cyclin E or ectopic overexpression of p21 rescued Bmi-1 deficiency-induced chromosome breaks. We therefore conclude that p21/cyclin E pathway is crucial in modulating the anticlastogenic function of Bmi-1. As it is well established that the overexpression of cyclin E potently induces genome instability and p21 suppresses the function of cyclin E, the novel and important implication from our findings is that Bmi-1 plays an important role in limiting genomic instability in cylin E-overexpressing cancer cells by positive regulation of p21. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00207136
- Volume :
- 136
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- International Journal of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 100320079
- Full Text :
- https://doi.org/10.1002/ijc.29114