THE P53 IGF-1 RECEPTOR AXIS IN THE REGULATION OF PROGRAMMED CELL-DEATH/

The loss or functional inactivation of tumor suppressor genes appears to be one of the most fundamental genetic mechanisms of tumorigenesis, and rational insights into the signaling pathways of tumor suppressor genes have emerged as a successful strategy of identifying novel drug discovery targets downstream of the tumor suppressor protein itself, Elucidation of novel pathways downstream of p53 have established a lin k between this important tumor suppressor gene and the insulin-like gr owth factor-1 receptor (IGF-1r), either via direct regulation of IGF-1 receptor levels, or modulation of IGFs via transactivation of the ins ulin-like growth factor-binding protein 3 (IGF-BP3) gene, Binding of I GF-BP3 to IGFs inhibits both their mitogenic and cell survival functio ns, highlighting a novel pathway whereby p53 may regulate apoptosis in tumor cells.