BAG2 is a target of the c-Myc gene and is involved in cellular senescence via the p21(CIP1) pathway

Cancer Lett. 2012 May 1;318(1):34-41. doi: 10.1016/j.canlet.2011.11.033. Epub 2011 Dec 4.

Abstract

Suppression of c-Myc is likely to induce cellular senescence in many tumors with unclear mechanisms. A proteomics survey indicated that high levels of BCL2-associated athanogene 2 (BAG2) were found in response to c-Myc repression in TRE293 cells. This observation led to the investigation into the role of BAG2 in c-Myc-induced senescence. The association of the c-Myc/SP1 complex with the BAG2 promoter verified the role of c-Myc/SP1 in regulating BAG2 transcription. Furthermore, high levels of BAG2 were found to induce p21(CIP1)-dependent senescence and subsequent carcinogenetic arrest, suggesting its possible role as an indirect activator of the p21(CIP1) pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Proliferation
  • Cellular Senescence*
  • Chromatin Immunoprecipitation
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Fluorescent Antibody Technique
  • Humans
  • Immunoenzyme Techniques
  • Immunoprecipitation
  • Luciferases / metabolism
  • Mice
  • Mice, Nude
  • Molecular Chaperones / genetics*
  • Molecular Chaperones / metabolism
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins c-myc / antagonists & inhibitors
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism
  • Spectrometry, Mass, Electrospray Ionization
  • Transcription, Genetic*
  • Tumor Cells, Cultured

Substances

  • BAG2 protein, human
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Molecular Chaperones
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • RNA, Small Interfering
  • Sp1 Transcription Factor
  • Luciferases