Reduced association of anti-apoptotic protein Mcl-1 with E3 ligase Mule increases the stability of Mcl-1 in breast cancer cells
2011

Stability of anti-apoptotic proteins in breast cancer

publication Evidence: moderate

Author Information

Author(s): Pervin S, Tran A, Tran L, Urman R, Braga M, Chaudhuri G, Singh R

Primary Institution: Charles Drew University of Medicine and Science

Hypothesis

The study investigates the mechanisms that increase the stability of anti-apoptotic proteins in breast cancer cells.

Conclusion

Reduced association of the Mule/Mcl-1 complex plays a significant role in increasing the stability of Mcl-1 in breast cancer cells, contributing to their resistance to apoptosis.

Supporting Evidence

  • Breast cancer cells showed reduced ubiquitination of Mcl-1 compared to normal mammary epithelial cells.
  • Transient association of Mcl-1 with E3 ligase Mule was observed in breast cancer cells.
  • Downregulation of pERK1/2 in breast cancer cells increased Mcl-1 levels and the Mcl-1/Mule complex.

Takeaway

Breast cancer cells are better at surviving because they keep a protein called Mcl-1 around longer, which helps them avoid dying when they should.

Methodology

The study used human mammary epithelial and established breast cancer cell lines, employing caspase assays, western blotting, small-interfering RNA treatment, and immunoprecipitation to assess protein stability.

Statistical Information

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1038/bjc.2011.242

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