Induction of G1 arrest by down-regulation of cyclin D3 in T cell hybridomas

J Exp Med. 1995 Aug 1;182(2):401-8. doi: 10.1084/jem.182.2.401.

Abstract

The relationship between activation-induced growth inhibition and regulation of the cell cycle progression was investigated in T cell hybridomas by studying the function of the cell cycle-regulating genes such as G1 cyclins and their associated kinases. Activation of T cell hybridomas by anti-T cell receptor antibody induces growth arrest at G1 phase of the cell cycle and subsequently results in activation-driven cell death. Rapid reduction of both messenger RNA and protein level of the cyclin D3 is accompanied by growth arrest upon activation. Although the residual cyclin D3 protein forms a complex with cdk4 protein, cyclin D3-dependent kinase activity is severely impaired. Stable transfectants engineered to express cyclin D3 override the growth arrest upon activation. These results imply that the activation signal through T cell receptor induces the down-regulation of cyclin D3 expression and cyclin D3-dependent kinase activity, leading to growth arrest in G1 phase of the cell cycle in T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • CDC2-CDC28 Kinases*
  • Cell Cycle*
  • Cell Death
  • Cyclin D2
  • Cyclin D3
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / metabolism*
  • DNA Primers / chemistry
  • Hybridomas / cytology*
  • In Vitro Techniques
  • Lymphocyte Activation*
  • Mice
  • Molecular Sequence Data
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins*
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction
  • T-Lymphocytes / cytology*

Substances

  • Ccnd2 protein, mouse
  • Ccnd3 protein, mouse
  • Cyclin D2
  • Cyclin D3
  • Cyclins
  • DNA Primers
  • Proto-Oncogene Proteins
  • Receptors, Antigen, T-Cell
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • Cdk2 protein, mouse
  • Cdk4 protein, mouse
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases