S100B Protein Down-Regulates p53 and Apoptosis in Malignant Melanoma

Strategic Insights -

New research from the University States reveals that the calcium-binding protein S100B plays a critical role in malignant melanoma by down-regulating the tumor suppressor protein p53 and reducing apoptosis. According to the study, published in the Journal of Biological Chemistry, S100B expression was inhibited in C8146A malignant melanoma cells using siRNA, leading to increased p53 protein and phosphorylated p53 levels, as well as restored p53-dependent apoptosis. This study provides new insights into the molecular mechanisms of malignant melanoma and suggests that S100B may be a potential therapeutic target for the treatment of this disease.

Key Takeaways:

  • The S100B-p53 protein complex was discovered in C8146A malignant melanoma cells, and the consequences of this interaction were further studied.
  • Inhibiting S100B expression in C8146A cells using siRNA increased p53 protein and phosphorylated p53 levels.
  • Restored p53-dependent apoptosis was observed in C8146A cells after siRNA(S100B) transfections, as evidenced by poly(ADP-ribose) polymerase cleavage, DNA ladder formation, caspase 3 and 8 activation, and aggregation of the Fas death receptor (+UV).
  • S100B-mediated apoptosis was independent of the mitochondria, as no changes were observed in mitochondrial membrane potential, cytochrome c release, caspase 9 activation, or ratios of pro-and anti-apoptotic proteins (BAX, Bcl-2, and Bcl-X(L)).
  • Cells lacking S100B (LOX-IM VI) were not affected by siRNA(S100B), and introduction of S100B reduced their UV-induced apoptosis activity by 7-fold.
  • S100B was found to contribute to cell survival in wild-type p53 cells (C8146A, UACC-2571, and UACC-62) after UV treatment.
  • Reducing S100B expression with siRNA was sufficient to activate p53, its transcriptional activation activities, and p53-dependent apoptosis pathway(s) in melanoma involving the Fas death receptor and perhaps PIDD.
  • A well-known marker for malignant melanoma, S100B, likely contributes to cancer progression by down-regulating the tumor suppressor protein, p53.

Statistics:

  • 7-fold reduction in UV-induced apoptosis activity in LOX-IM VI cells after introduction of S100B.
  • 27487-98: The journal article reference number.
  • 35: The volume number of the Journal of Biological Chemistry.
  • 2010: The year the study was published.

Sources:

  • Lin, J., et al. (2010). The calcium-binding protein S100B down-regulates p53 and apoptosis in malignant melanoma. Journal of Biological Chemistry, 285(35), 27487-98.
  • Carrier Proteins. (n.d.). Retrieved from
  • Biotech Week editors. (2010, September 17). New investigation results, 'The calcium-binding protein S100B down-regulates p53 and apoptosis in malignant melanoma,' are detailed in a study published in Journal of Biological Chemistry. Biotech Week.