The von Hippel-Lindau protein pVHL inhibits ribosome biogenesis and protein synthesis.

TitleThe von Hippel-Lindau protein pVHL inhibits ribosome biogenesis and protein synthesis.
Publication TypeJournal Article
Year of Publication2013
AuthorsZhao W-T, Zhou C-F, Li X-B, Zhang Y-F, Fan L, Pelletier J, Fang J
JournalThe Journal of biological chemistry
Volume288
Issue23
Pagination16588-97
Date Published2013 Jun 7
Abstract

pVHL, the product of von Hippel-Lindau (VHL) tumor suppressor gene, functions as the substrate recognition component of an E3-ubiquitin ligase complex that targets hypoxia inducible factor α (HIF-α) for ubiquitination and degradation. Besides HIF-α, pVHL also interacts with other proteins and has multiple functions. Here, we report that pVHL inhibits ribosome biogenesis and protein synthesis. We find that pVHL associates with the 40S ribosomal protein S3 (RPS3) but does not target it for destruction. Rather, the pVHL-RPS3 association interferes with the interaction between RPS3 and RPS2. Expression of pVHL also leads to nuclear retention of pre-40S ribosomal subunits, diminishing polysomes and 18S rRNA levels. We also demonstrate that pVHL suppresses both cap-dependent and cap-independent protein synthesis. Our findings unravel a novel function of pVHL and provide insight into the regulation of ribosome biogenesis by the tumor suppressor pVHL.

DOI10.1155/2013/384125
Alternate JournalJ. Biol. Chem.