Regulation of Retinoblastoma Protein Functions by Ectopic Expression of Human Cyclins

Cell. 1992 Sep 18;70(6):993-1006. doi: 10.1016/0092-8674(92)90249-c.

Abstract

The retinoblastoma susceptibility gene (RB) product, the retinoblastoma protein (pRb), functions as a regulator of cell proliferation. Introduction of the RB gene into SAOS-2 osteosarcoma cells, which lack functional pRb, prevents cell cycle progression. Such growth-suppressive functions can be modulated by phosphorylation of pRb, which occurs via cell cycle-regulated kinases. We show that constitutively expressed cyclins A and E can overcome pRb-mediated suppression of proliferation. pRb becomes hyperphosphorylated in cells overexpressing these cyclins, and this phosphorylation is essential for cyclin A- and cyclin E-mediated rescue of pRb-blocked cells. This suggests that G1 and S phase cyclins can act as regulators of pRb function in the cell cycle by promoting pRb phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Nucleus
  • Cyclins / metabolism
  • Cyclins / physiology*
  • G1 Phase / physiology
  • Gene Expression
  • Genetic Vectors
  • Humans
  • Mutation
  • Phenotype
  • Phosphorylation
  • Protein Kinases
  • Recombinant Proteins
  • Retinoblastoma Protein / physiology*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Cyclins
  • Recombinant Proteins
  • Retinoblastoma Protein
  • Protein Kinases