p202 levels are negatively regulated by serum growth factors

p202 is an IFN-inducible phosphoprotein (M-r 52,000) whose expression in tr ansfected cells retards proliferation. Interestingly, the reduced levels of p202 in fibroblasts tin consequence of the expression of antisense to 202 RNA), under reduced serum conditions, increase the susceptibility of cells to apoptosis, To identify the functional role of p202 in cell growth regula tion, we tested whether serum growth factor levels in the culture medium af fect p202 levels. Here we report that, under reduced serum conditions, the p202 levels were increased in fibroblasts, and the increase was seen at bot h the mRNA and protein levels. Moreover, an increase in p202 levels was cor related with cell growth arrest in the G(1) phase of the cell cycle. Intere stingly, the presence of platelet-derived growth factor AB, basic fibroblas t growth factor, or transforming growth factor pi in the culture medium abr ogated the increase in p202 levels seen under reduced serum conditions. We found that the increase in p202 levels was accompanied by an increase in Ju nD/activation protein 1 (AP-1) levels, and transfection of a JunD-encoding plasmid along with a reporter plasmid in which transcription of the reporte r gene (luciferase) was driven by the 5'-regulatory region of the 202 gene resulted in an increase in the activity of luciferase, Additionally, stable overexpression of JunD in cells, under reduced serum conditions, also resu lted in an increase in p202 levels, Interestingly, one of the AP-l-like DNA -binding sequences present in the 5'-regulatory region of the 202 gene coul d selectively bind to the JunD/AP-1 transcription factor. Taken together, o ur observations reported herein suggest that in fibroblasts, under reduced serum conditions, the increased levels of JunD/AP-1 contribute to the trans criptional up-regulation of p202 levels, which may be important for the reg ulation of apoptosis.