ABSTRACT
A growing body of evidences indicate that deregulation of translation contributes to tumourigenesis. In tumours, alterations of translational control of specific mRNAs encoding oncogenes or tumour suppressors have been extensively reported. Moreover, restricting the rate of protein synthesis has been shown to delays tumourigenesis in C-Myc overexpressing or PTEN deleted mice models. Finally, the specific inhibition of RNA polymerase I (RNA pol I) has been shown to kill cancer cells without affecting normal cells. It thus emerges that a tight coordination between the rate of global protein synthesis and a defined translational program is required to prevent tumour development. In this review, we expose the evidences supporting that p53 acts as a translational regulator. In addition, this review discusses the notion that the ability to maintain both a selective translational program and a low level of protein synthesis could directly contribute to the p53 tumour-suppressor activity.
Subject(s)
Genes, Tumor Suppressor/physiology , Neoplasms/genetics , Tumor Suppressor Protein p53/genetics , Animals , Carcinogenesis/genetics , Humans , Protein Biosynthesis/genetics , RNA, Messenger/geneticsABSTRACT
In healthy cells, fusion and fission events participate in regulating mitochondrial morphology. Disintegration of the mitochondrial reticulum into multiple punctiform organelles during apoptosis led us to examine the role of Drp1, a dynamin-related protein that mediates outer mitochondrial membrane fission. Upon induction of apoptosis, Drp1 translocates from the cytosol to mitochondria, where it preferentially localizes to potential sites of organelle division. Inhibition of Drp1 by overexpression of a dominant-negative mutant counteracts the conversion to a punctiform mitochondrial phenotype, prevents the loss of the mitochondrial membrane potential and the release of cytochrome c, and reveals a reproducible swelling of the organelles. Remarkably, inhibition of Drp1 blocks cell death, implicating mitochondrial fission as an important step in apoptosis.