p53: guardian of ploidy

Mol Oncol. 2011 Aug;5(4):315-23. doi: 10.1016/j.molonc.2011.07.007. Epub 2011 Jul 30.

Abstract

Aneuploidy, often preceded by tetraploidy, is one of the hallmarks of solid tumors. Indeed, both aneuploidy and tetraploidy are oncogenic occurrences that are sufficient to drive neoplastic transformation and cancer progression. True to form, the tumor suppressor p53 obstructs propagation of these dangerous chromosomal events by either instigating irreversible cell cycle arrest or apoptosis. The tumor suppressor Lats2, along with other tumor inhibitory proteins such as BRCA1/2 and BubR1, are central to p53-dependent elimination of tetraploid cells. Not surprisingly, these proteins are frequently inactivated or downregulated in tumors, synergizing with p53 inactivation to establish an atmosphere of "tolerance" for a non-diploid state.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aneuploidy*
  • Animals
  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism
  • BRCA2 Protein / genetics
  • BRCA2 Protein / metabolism
  • Cell Cycle Checkpoints
  • Cell Transformation, Neoplastic
  • Disease Progression
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Tetraploidy*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • LATS2 protein, human
  • BUB1 protein, human
  • Bub1 spindle checkpoint protein
  • Protein-Serine-Threonine Kinases