RGS19 stimulates cell proliferation by deregulating cell cycle control and enhancing Akt signaling

Cancer Lett. 2011 Oct 28;309(2):199-208. doi: 10.1016/j.canlet.2011.06.002. Epub 2011 Jun 25.

Abstract

RGS19 is a regulator of G protein signaling which is upregulated in ovarian cancers and its overexpression promotes cell proliferation in several mammalian cell types. Here we showed that cyclin D1/3 and Cdk6 were upregulated in HEK293 cells overexpressing RGS19, while INK4A and INK4B were reduced. Moreover, RGS19 augmented serum-stimulated PTEN/PDK/Akt and Rb phosphorylations in 293/RGS19 and Caco2/RGS19 cells. These changes were reversed upon the knockdown of RGS19. Consistent with an elevated Akt activity, increased levels of phosphorylated Bad and c-Raf and a diminished expression of TSC2 were detected, thus demonstrating that RGS19 can deregulate cell proliferation via multiple pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle*
  • Cell Proliferation*
  • Cyclin D1 / biosynthesis
  • Cyclin D1 / genetics
  • Cyclin D3 / biosynthesis
  • Cyclin D3 / genetics
  • Cyclin-Dependent Kinase 6 / biosynthesis
  • Cyclin-Dependent Kinase 6 / genetics
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • PTEN Phosphohydrolase / metabolism
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-raf / biosynthesis
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • RGS Proteins / biosynthesis
  • RGS Proteins / genetics
  • RGS Proteins / metabolism*
  • RNA Interference
  • RNA, Small Interfering
  • Signal Transduction
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins / biosynthesis
  • bcl-Associated Death Protein / biosynthesis

Substances

  • BAD protein, human
  • CDKN2B protein, human
  • Cyclin D3
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • RGS Proteins
  • RNA, Small Interfering
  • TSC2 protein, human
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins
  • bcl-Associated Death Protein
  • regulator of G-protein signalling 19
  • Cyclin D1
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-raf
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6
  • PTEN Phosphohydrolase
  • PTEN protein, human