Hsp90 Cleavage by Oxidative Stress Leads to Cancer Cell Death

Strategic Insights -

Researchers at the University of Louvain in Brussels, Belgium have made a significant discovery about the heat shock protein 90 (Hsp90) and its role in cancer cell death. They found that an oxidative stress generated by ascorbate/menadione redox cycling leads to Hsp90 cleavage, resulting in the degradation of critical proteins and ultimately, cancer cell death.

Key Takeaways:

  • The heat shock protein 90 (Hsp90) plays a crucial role in the stability of several proteins essential for malignant transformation, making it an interesting therapeutic target for cancer therapy.
  • An oxidative stress generated by ascorbate/menadione redox cycling affects Hsp90, leading to the degradation of some critical proteins and cell death.
  • Unlike 17-AAG, which inhibits Hsp90 but enhances Hsp70 levels, ascorbate/menadione-treated cells present an additional Hsp90 protein band of about 70kDa, suggesting Hsp90 cleavage.
  • The site of Hsp90 cleavage is located at its N-terminal part, and the beta-Hsp90 isoform is cleaved while the alpha isoform is down-regulated.
  • The degradation of Hsp90 client proteins, such as Bcr-Abl, RIP, and Akt, was observed in K562 leukemia cells exposed to oxidative stress.
  • Hsp90 cleavage and client protein degradation were also observed in KU812 leukemia cells treated with ascorbate/menadione.
  • The researchers concluded that due to the major role of Hsp90 in stabilizing oncogenic and mutated proteins, these results may have potential clinical applications.

Statistics:

  • 70kDa: the molecular weight of the additional Hsp90 protein band observed in ascorbate/menadione-treated cells.
  • 3:3: the volume and issue number of the Biochemical Pharmacology journal article.
  • 375-83: the page numbers of the Biochemical Pharmacology journal article.

Sources:

  • Beck, R. et al. (2009) Hsp90 cleavage by an oxidative stress leads to its client proteins degradation and cancer cell death. Biochemical Pharmacology, 77(3), 375-83.
  • University catholique of Louvain (2009) Hsp90 cleavage by oxidative stress leads to cancer cell death, Available from:
  • Cancer Weekly (2009) Hsp90 cleavage by oxidative stress leads to cancer cell death, Available from: