Em. Ruaro et al., A PROLINE-RICH MOTIF IN P53 IS REQUIRED FOR TRANSACTIVATION-INDEPENDENT GROWTH ARREST AS INDUCED BY GAS1, Proceedings of the National Academy of Sciences of the United Statesof America, 94(9), 1997, pp. 4675-4680
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.