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Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
10:00

Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling

Published on: October 28, 2014

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

Wen-Ting Zhao1, Cheng-Fu Zhou2, Xue-Bing Li1

  • 1Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

The Journal of Biological Chemistry
|April 25, 2013
PubMed

Insights

The von Hippel-Lindau (VHL) tumor suppressor protein (pVHL) inhibits ribosome biogenesis and protein synthesis. This novel function of pVHL provides insight into cellular regulation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Biology

Background:

  • The von Hippel-Lindau (VHL) tumor suppressor gene product, pVHL, is known to target hypoxia-inducible factor α (HIF-α) for degradation.
  • pVHL has diverse functions beyond its role in the VHL E3-ubiquitin ligase complex.

Purpose of the Study:

  • To investigate the novel function of pVHL in regulating ribosome biogenesis and protein synthesis.
  • To elucidate the molecular mechanisms by which pVHL affects these cellular processes.

Main Methods:

  • Co-immunoprecipitation assays to detect protein interactions.
  • Analysis of ribosomal subunit assembly and rRNA levels.
  • Assessment of both cap-dependent and cap-independent protein synthesis.

Main Results:

  • pVHL associates with the 40S ribosomal protein RPS3, interfering with RPS3-RPS2 interaction.
  • Expression of pVHL causes nuclear retention of pre-40S ribosomal subunits, reducing polysomes and 18S rRNA.
  • pVHL suppresses both cap-dependent and cap-independent protein synthesis.

Conclusions:

  • pVHL possesses a previously unrecognized role in inhibiting ribosome biogenesis and protein synthesis.
  • The interaction of pVHL with RPS3 is a key mechanism for this inhibitory function.
  • These findings reveal a new regulatory pathway involving the tumor suppressor pVHL in controlling protein production.
Keywords:
Cancer BiologyProtein SynthesisRibosome AssemblyRibosomesTumorpVHL

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