A PROLINE-RICH MOTIF IN P53 IS REQUIRED FOR TRANSACTIVATION-INDEPENDENT GROWTH ARREST AS INDUCED BY GAS1

The involvement of p53 in regulating diverse cellular processes dictat es that it must respond to multiple signaling mechanisms, thus coordin ating the response to various ''stress conditions.'' Genotoxic stress has served as a paradigm to dissect the transactivation-dependent bran ch of the pathway by which p53 can induce growth arrest, Alternate mec hanisms have been invoked to explain transactivation-independent effec ts of p53, especially in the context of apoptosis, We have identified a p53-dependent pathway initiated by the gas1 product, a plasma membra ne protein highly expressed during GO, which activates a transactivati on-independent p53 growth arrest function. Through a detailed deletion al analysis and site-specific mutagenesis of p53 we show that the Gas1 -dependent signal transduction relies on a proline-rich region (amino acids 63-85) of murine p53, In vivo competition experiments using comb inations of such mutants implicate this functional domain of p53 as a docking site in the transmission of antiproliferative signals.