Co-operation of simian virus 40 T antigen and insulin receptor substrate-1 in protection from apoptosis induced by interleukin-3 withdrawal

Oncogene. 1997 Aug 18;15(8):961-70. doi: 10.1038/sj.onc.1201265.

Abstract

32D cells are interleukin-3 (IL-3) dependent murine hemopoietic cells, that undergo apoptosis after IL-3 withdrawal. An overexpressed insulin-like growth factor I receptor (IGF-IR) protects these cells from apoptosis induced by IL-3 withdrawal. When 32D cells are stably transfected with plasmids expressing either IRS-1 (a major substrate of the IGF-IR) or the Simian virus 40 large T antigen, singly, they still undergo apoptosis after IL-3 withdrawal, although IRS-1 offers partial protection. The cells, however, are fully protected when they are stably transfected with both IRS-1 and SV40 T antigen. Protection from apoptosis in these cells is characterized by the stabilization of the Stat1 and Stat5 protein levels, whose synthesis is inhibited when IL-3 is withdrawn.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Polyomavirus Transforming / pharmacology
  • Antigens, Polyomavirus Transforming / physiology*
  • Apoptosis*
  • Cell Division
  • Cell Line / drug effects
  • DNA-Binding Proteins / biosynthesis
  • Insulin Receptor Substrate Proteins
  • Interleukin-3 / pharmacology*
  • Methionine / analysis
  • Mice
  • Milk Proteins*
  • Phosphoproteins / pharmacology
  • Phosphoproteins / physiology*
  • Plasmids
  • STAT1 Transcription Factor
  • STAT5 Transcription Factor
  • Trans-Activators / biosynthesis
  • Transfection

Substances

  • Antigens, Polyomavirus Transforming
  • DNA-Binding Proteins
  • Insulin Receptor Substrate Proteins
  • Interleukin-3
  • Irs1 protein, mouse
  • Milk Proteins
  • Phosphoproteins
  • STAT1 Transcription Factor
  • STAT5 Transcription Factor
  • Stat1 protein, mouse
  • Trans-Activators
  • Methionine