Shaping the p53 response with nucleoporins

Abstract

In this issue, Singer et al. (2012) reveal that the nucleoporin Nup98 supports adaptation to genotoxic stress by protecting specific p53-induced mRNAs from exosome-dependent degradation, suggesting that wild-type Nup98 may possess tumor suppressor function.

Figure 1. Nup98 Regulates the Stability of Selected p53-Induced mRNAs and Possibly Suppresses Tumorigenesis

In response to genotoxic stimuli, the tumor suppressor protein p53 upregulates target genes such as p21 to regulate the cell cycle and DNA repair. In normal cells, the interaction of Nup98 with the 3′UTR of p21 mRNA protects p21 from degradation. In the absence of Nup98, the exposed p21 mRNA is targeted for exosome-mediated degradation. Singer et al. (2012) showed that downregulation of Nup98 expression occurs in some types of cancer, which may lead to destabilization of selected p53 target mRNAs, contributing to tumorigenesis.