A nuclear pore component regulates select p53 target genes

Abstract

Alhough many studies have focused on specific transcriptional programs regulated by p53 in response to different stresses, p53 target gene preference is still poorly defined and may rely on additional modes of regulation. Here, we demonstrate that the nucleoporin Nup98 is required for full expression of key effectors of the p53 pathway, such as p21, by a process that occurs post-transcriptionally. Nup98 associates with the 3’-UTR of p21 mRNA and protects it from degradation by the exosome. An in silico approach reveals that also other p53 target genes (e.g. 14–3–3 sigma) are similarly regulated by Nup98. Expression of Nup98 is correlated with p21 on mRNA level in a cohort of hepatocellular carcinoma patients (n=27, r=0.52), supporting the in vivo relevance of our findings. Our study elucidates a previously unrecognized function of Nup98 in hepatocarcinogenesis distinct from the well-characterized oncogenic properties of Nup98 fusion proteins such as Nup98-HOXA9 in leukemogenesis.