COOPERATION 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 insuli n-like growth factor I receptor (IGF-IR) protects these cells from apo ptosis induced by IL-3 withdrawal. When 32D cells are stably transfect ed with plasmids expressing either IRS-1 (a major substrate of the IGF -IR) or the Simian virus 40 large T antigen, singly, they still underg o apoptosis after IL-3 withdrawal, although IRS-1 offers partial prote ction. The cells, however, are fully protected when they are stably tr ansfected with both IRS-1 and SV40 T antigen. Protection from apoptosi s in these cells is characterized by the stabilization of the Stat1 an d Stat5 protein levels, whose synthesis is inhibited when IL-3 is with drawn.