Skp2B Overexpression Alters a Prohibitin-p53 Axis and the Transcription of PAPP-A, the Protease of Insulin-Like Growth Factor Binding Protein 4
2011

Skp2B Overexpression Affects p53 and PAPP-A in Breast Cancer

publication Evidence: moderate

Author Information

Author(s): Chander Harish, Halpern Max, Resnick-Silverman Lois, Manfredi James J., Germain Doris

Primary Institution: Mount Sinai School of Medicine, New York, New York, United States of America

Hypothesis

Is there a link between p53 activity and the proteolysis of IGFBP-4 in breast cancer?

Conclusion

The study reveals that prohibitin acts as a chaperone for p53, and its degradation by Skp2B leads to increased PAPP-A levels and IGFBP-4 cleavage, contributing to breast cancer progression.

Supporting Evidence

  • Skp2B overexpression leads to increased levels of PAPP-A.
  • Wild type p53 represses PAPP-A transcription, while mutant p53 activates it.
  • Prohibitin is necessary for maintaining the proper conformation of p53.

Takeaway

When a protein called prohibitin is reduced, another protein called p53 can get messed up, which leads to changes that can cause breast cancer.

Methodology

The study used transgenic mice and various cell lines to analyze the effects of Skp2B overexpression on p53 and PAPP-A levels.

Statistical Information

P-Value

p<0.0001

Statistical Significance

p<0.0001

Digital Object Identifier (DOI)

10.1371/journal.pone.0022456

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