Programmed cell death

Apoptosis, or programmed cell death, is the fundamental biological process coordinately regulated by several energy-dependent biochemical mechanisms that mediate characteristic morphological changes prior to the death of the cell. The dysregulation of apoptosis has been directly implicated in the development of a cancer, and therefore the elucidation of the signaling pathways that control apoptosis is a critical area of cancer research.1

A variety of different types of cancers have been reported to exhibit inactivation or mutation of the tumor suppressor protein p53, a key promoter of apoptosis.2‑4 Other various proteins are themselves regulators of p53 activity such as the ubiquitin ligase MDM2, an enzyme that has been shown to mark p53 for proteolytic degradation by the proteasome.5,6

MDM2 protein expression is elevated in many forms of cancer, and the directed overexpression of MDM2 has been reported to foster the development of cancerous cells.7‑11 Thus, increased expression and/or activity of MDM2 in cancerous cells may promote the down-regulation of p53 protein expression, thereby potentially disabling the ability of p53 to properly regulate the apoptotic cell death program.7‑9,11

  1. Cotter TG. Nat Rev Cancer. 2009;9:501-507.
  2. Brown CJ, et al. Nat Rev Cancer. 2009;9:862-873.
  3. Goldstein I. et. al. Cancer Gene Ther. 2011;18:2-11.
  4. Zhu Y. et. al. Cancer Cell. 2005;8:19-130
  5. Kubbutat MH. et. al. Nature. 1997;387:299-303.
  6. Itahana K. et. al. Cancer Cell. 2007;12:355-66.
  7. Leach FS. et. al. Cancer Res. 1993;53:2231-2234.
  8. Watanabe T. et. al. Blood. 1994;84:3158-3165.
  9. McCann AH et. al. Br J Cancer. 1995;71:981-985.
  10. Fakharzadeh SS. et. al. EMBO J. 1991;10:1565-1569.
  11. Wade M. et. al. Nat Rev Cancer. 2013;13:83-96.

Targeting the MDM2-p53 Protein Interaction as a Novel Therapeutic Strategy in Cancer ->