THE INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR AS A PHYSIOLOGICALLY RELEVANT TARGET OF P53 IN APOPTOSIS CAUSED BY INTERLEUKIN-3 WITHDRAWAL

The wild-type p53 protein is known to modulate apoptosis induced in 32 D murine hemopoietic cells by interleukin-3 withdrawal. In 32D cells a nd in 32D cells constitutively expressing a temperature-sensitive muta nt of p53 (32Dtsp53), overexpression of a wild-type (but not a mutant) insulin-like growth factor I receptor (IGF-IR) protects these cells f rom apoptosis, A tsp53 in its wild-type conformation causes a decrease in the levels of IGF-IRs, and this decrease is accompanied by increas ed sensitivity of these cells to apoptosis. However, when the expressi on of the IGF-IR cDNA is regulated by a viral promoter, IGF-IR levels are not decreased by a wild-type p53, and apoptosis does not occur, Th ese findings show that, in 32Dtsp53 cells, the IGF-IR is a physiologic ally relevant target of p53 in the process of apoptosis.