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

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is characterized by the stabilization of the Stat1 and Stat5 protein levels, whose synthesis is inhibited when IL-3 is withdrawn.