Regulation of protein synthesis by inducible wild-type p53 in human lung carcinoma cells.

Activation of an over-expressed mutant form of the tumour suppressor protein p53 has been shown to inhibit protein synthesis. To determine whether this effect is due only to high level expression or the mutant nature of the protein, we have used a doxycycline-inducible lung carcinoma cell line capable of expressing wild-type p53. We now show that levels of wild-type p53 similar to those expressed endogenously also inhibit protein synthesis. The mechanism involves dephosphorylation and accumulation of the translational inhibitor 4E-BP1, and increased association of 4E-BP1 with initiation factor eIF4E. The inhibition of translation is not a consequence of p53-mediated apoptosis.