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pubmed:abstractText |
The polycomb group protein BMI1 has been linked to proliferation, senescence, cancer progression and stem cell phenotype. At present, very little is known about its regulation. Here, we report that BMI1 contains a functional recognition motif for the F box protein ?TrCP, which regulates ubiquitination and proteasome-mediated degradation of various proteins. We show that overexpression of wild-type ?TrCP but not the ?F mutant of it promotes BMI1 ubiquitination and degradation, and knockdown of ?TrCP results in increased expression of BMI1. Furthermore, a mutant of BMI1 with an altered ?TrCP recognition motif is much more stable than wild-type BMI1. We also show that wild-type BMI1 but not the mutant BMI1 interacts with ?TrCP. Accordingly, compared to wild-type BMI1, mutant protein exhibited increased pro-oncogenic activity. In summary, our findings suggest that ?TrCP regulates turnover of BMI1 and its function relevant to oncogenesis, cellular senescence and aging.
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