Architecture of the nuclease module of the yeast Ccr4-not complex: the Not1-Caf1-Ccr4 interaction.

Shortening eukaryotic poly(A) tails represses mRNA translation and induces mRNA turnover. The major cytoplasmic deadenylase, the Ccr4-Not complex, is a conserved multisubunit assembly. Ccr4-Not is organized around Not1, a large scaffold protein that recruits two 3'-5' exoribonucleases, Caf1 and Ccr4.

Pyrimidine biosynthesis links mitochondrial respiration to the p53 pathway.

While many functions of the p53 tumor suppressor affect mitochondrial processes, the role of altered mitochondrial physiology in a modulation of p53 response remains unclear. As mitochondrial respiration is affected in many pathologic conditions such as hypoxia and intoxications, the impaired electron transport chain could emit additional p53-inducing signals and thereby contribute to tissue damage. Here we show that a shutdown of mitochondrial respiration per se does not trigger p53 response, because inhibitors acting in the proximal and distal segments of the respiratory chain do not activate p53.