Studies demonstrating the complexity of regulation and action of the growth inhibitory gene SDI1

The identification of the DNA synthesis inhibitory gene SDI1 by investigators studying cell senescence, tumor suppression, cell cycle control and differentiation suggest a key regulatory role for this gene. To better understand the growth regulatory activity of this gene we proceeded with the experiments described here. The data demonstrate that SDI1 is an important downstream effector of p53, but here we report that it can also cause inhibition of DNA synthesis in several immortal human cell lines, independent of p53 or Rb status. Levels of SDI1 mRNA expression in immortal cells are consistently much lower than that of normal cells, indicating that immortalization is not compatible with high expression of SDI1. These results highlight the complex nature of regulation of this gene and its mode of action.