Interleukin-1 (IL-1) causes G1-phase growth arrest of A375-C6 human melanoma cells by hypophosphorylation of the retinoblastoma susceptibility gene product Rb. Because p53 and p21/WAF1 proteins are key components of growth arrest pathways involving Rb hypophosphorylation, we tested the functional role of these two proteins in IL-1 action. Exposure to IL-1 caused induction of both p53 and p21/WAF1 proteins. However, inhibition of p53 function by the K1 mutant of SV40-T antigen or by m175 (Arg to His) dominant- negative mutant of p53 did not result in abrogation of IL-1 action, suggesting that p53 function is not required for growth arrest by IL-1. Studies aimed at testing the role of p21/WAF1 in IL-1 action indicated that IL-1 induced p21/WAF1 expression independently of the p53 status of the cells. However, inhibition of p21/WAF1 expression resulted in only a marginal rescue from the growth-arresting action of IL-1. These findings imply that despite their induction, neither wild-type p53 nor p21 can fully account for the growth arrest by IL-1. Thus, a p53-and p21-independent pathway(s) mediates IL-1 action.
|Number of pages||7|
|Journal||Journal of Biological Chemistry|
|State||Published - Nov 13 1998|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology