title: p21/Cyclin E pathway modulates anticlastogenic function of Bmi-1 in cancer cells.
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.
authors.affiliation: School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Department of Anatomy and Center for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Deng
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Agnes F Y
authors.initials: AF
authors.lastname: Tiwari
authors.forename: Hang
authors.initials: H
authors.lastname: Su
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhu
authors.forename: Victoria Ming Yi
authors.initials: VM
authors.lastname: Lau
authors.forename: Pok Man
authors.initials: PM
authors.lastname: Hau
authors.forename: Yim Ling
authors.initials: YL
authors.lastname: Yip
authors.forename: Annie L M
authors.initials: AL
authors.lastname: Cheung
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
authors.forename: Sai Wah
authors.initials: SW
authors.lastname: Tsao
mesh_terms: D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D019927:Cyclin E / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000502:physiology*; D042822:Genomic Instability; D006801:Humans; D063150:Polycomb Repressive Complex 1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C069077:BMI1 protein, human; C493956:CDKN1A protein, human; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D063150:Polycomb Repressive Complex 1
keywords: Bmi-1; cyclin E; genomic instability; p21; replicative stress