p8 and prothymosin alpha: unity is strength.

Summary

p8 and prothymosin alpha are two natively unstructured proteins with anti-apoptotic activity. We showed that their interaction results in the formation of a one-to-one heterodimer complex with stable structure. To test whether the heterodimer bears the function previously attributed to both proteins, we monitored the consequences on apoptosis of modulating in vitro the concentrations of both proteins. Overexpression was obtained by transfection of appropriate vectors and inhibition by using specific siRNAs. In all conditions inhibition of apoptosis correlated with the level of the partner with lowest concentration, demonstrating that the anti-apoptotic effect previously attributed to each proteins was in fact borne by the p8/ProTalpha complex, the two proteins, being individually inactive. These results show that the function attributed to a natively unfolded protein might actually belong to a multi-protein complex in which the protein of interest is engaged.