Survivin inhibits anti-growth effect of p53 activated by aurora B

Biochem Biophys Res Commun. 2005 Nov 4;336(4):1164-71. doi: 10.1016/j.bbrc.2005.08.235.

Abstract

Genomic instability and apoptosis evasion are hallmarks of cancer, but the molecular mechanisms governing these processes remain elusive. Here, we found that survivin, a member of the apoptosis-inhibiting gene family, and aurora B kinase, a chromosomal passenger protein, were co-overexpressed in the various glioblastoma cell lines and tumors. Notably, exogenous introduction of the aurora B in human BJ cells was shown to decrease cell growth and increase the senescence-associated beta-galactosidase activity by activation of p53 tumor suppressor. However, aurora B overexpression failed to inhibit cell proliferation in BJ and U87MG cells transduced with dominant-negative p53 as well as in p53(-/-) mouse astrocytes. Aurora B was shown to increase centrosome amplification in the p53(-/-) astrocytes. Survivin was shown to induce anchorage-independent growth and inhibit anti-proliferation and drug-sensitive apoptosis caused by aurora B. Overexpression of both survivin and aurora B further accelerated the proliferation of BJ cells. Taken together, the present study indicates that survivin should accelerate tumorigenesis by inhibiting the anti-proliferative effect of p53 tumor suppressor that is activated by aurora B in normal and glioblastoma cells containing intact p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Astrocytes / metabolism
  • Aurora Kinase B
  • Aurora Kinases
  • Brain Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Centrosome / metabolism
  • Contact Inhibition / physiology
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Enzyme Activation
  • Genes, Reporter
  • Glioblastoma / metabolism
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Mice
  • Microtubule-Associated Proteins / biosynthesis
  • Microtubule-Associated Proteins / physiology*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / physiology*
  • Neoplasms / metabolism*
  • Phosphorylation
  • Protein Serine-Threonine Kinases / biosynthesis
  • Protein Serine-Threonine Kinases / physiology*
  • Survivin
  • Tumor Suppressor Protein p53 / antagonists & inhibitors*
  • Tumor Suppressor Protein p53 / physiology

Substances

  • BIRC5 protein, human
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Survivin
  • Tumor Suppressor Protein p53
  • AURKB protein, human
  • Aurkb protein, mouse
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases