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Published on: September 28, 2012
hBub1 negatively regulates p53 mediated early cell death upon mitotic checkpoint activation
Fangming Gao1, Jose F Ponte, Mary Levy
1Department of Medicine, Genetics Program and Cancer Research Center, Boston University School of Medicine, Boston, MA, USA.
Cancer Biology & Therapy
|March 3, 2009
Summary
The outer kinetochore protein hBub1 regulates p53-mediated cell death during the spindle assembly checkpoint (SAC). hBub1 inhibits apoptosis, suggesting a therapeutic target for cancer treatment.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Spindle assembly checkpoint (SAC) activation typically leads to cell cycle arrest.
- Previous studies indicated that hBub1 depletion during SAC activation promotes p53-mediated cell death over aneuploidy.
Purpose of the Study:
- To investigate the role of p53 phosphorylation at Ser37 in apoptosis upon SAC activation.
- To elucidate the interaction between hBub1 and p53 in response to mitotic spindle damage.
- To understand hBub1's function in regulating p53-mediated cell death.
Main Methods:
- Western blotting to detect p53 phosphorylation.
- Immunoprecipitation to confirm protein interactions.
- Quantitative PCR to assess target gene expression (PUMA, BAX).
Main Results:
- Phosphorylation of p53 at Ser37 is crucial for its proapoptotic function during SAC activation.
- hBub1 directly interacts with p53 at kinetochores following mitotic spindle damage.
- hBub1 inhibits the transactivation of proapoptotic genes PUMA and BAX by p53.
Conclusions:
- hBub1 functions as a negative regulator of p53-mediated early cell death in a novel SAC pathway.
- Targeting hBub1 could be a therapeutic strategy to induce apoptosis in p53-proficient cancer cells.
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