P53 REGULATION OF TRANSLATION

Case Western Reserve University, Cleveland OH

Investigators

Linked publications & trials

Abstract

The mechanism of translation has been well studied for decades. A function has been ascribed to nearly all know translation factors and methods of their regulation are beginning to be understood. Until recently the view of translation has been a static one, if regulation of gene expression occured it was a transcriptional mechanism. This view has been challenged by the fact that major changes in the translational machinery occur upon mitogenic stimulation. It is becoming increasingly clear that the regulation of translation through translation factor expression and phosphorylation is important for cell cycle events. The prototypical tumor suppressor protein p53 has also been demonstrated to be involved in the regulation of translation. p53 is associated with ribosomes and multiple cell cycle regulatory genes are translationally controlled in a p53-mediated manner. The use of a cell line harboring a temperature sensitive mutation of p53 has proven effective for studying p53-regulated transcription and apoptosis. The effect of p53 on the regulation of translation factors, through phosphorylation and expression will be studied in a similar manner. Additionally, multiple genes have been shown to be translationally regulated by p53, and studies will be undertaken to determine how p53 regulates the translation of these messages. As little is understood about translational regulation of cell cycle genes, as well as the role p53 plays in their translational regulation, the work proposed in this grant should open new avenues of investigation into these questions.