STUDIES DEMONSTRATING THE COMPLEXITY OF REGULATION AND ACTION OF THE GROWTH-INHIBITORY GENE SDI1

The identification of the DNA synthesis inhibitory gene SDII by invest igators studying cell senescence, tumor suppression, cell cycle contro l and differentiation suggest a key regulatory role for this gene. To better understand the growth regulatory activity of this gene we proce eded with the experiments described here, The data demonstrate that SD II is an important downstream effector of p53, but here we report that it can also cause inhibition of DNA synthesis in several immortal hum an cell lines, independent of p53 or Rb status. Levels of SDII mRNA ex pression in immortal cells are consistently much lower than that of no rmal cells, indicating that immortalization is not compatible with hig h expression of SDII. These results highlight the complex nature of re gulation of this gene and its mode of action.