The Von Hippel-Lindau Protein PVHL Inhibits Ribosome Biogenesis and Protein Synthesis

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2013 Apr 25

PMID 23612971

Citations 12

Authors

Wen-Ting Zhao

Cheng-Fu Zhou

Xue-Bing Li

Yun-Fang Zhang

Li Fan

Jerry Pelletier

Jing Fang

Affiliations

Soon will be listed here.

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.

Citing Articles

Rb1/Rbl1/Vhl loss induces mouse subretinal angiomatous proliferation and hemangioblastoma.

Wei R, Ren X, Kong H, Lv Z, Chen Y, Tang Y JCI Insight. 2019; 4(22).

PMID: 31613797 PMC: 6948866. DOI: 10.1172/jci.insight.127889.

Genotype-phenotype relations of the von Hippel-Lindau tumor suppressor inferred from a large-scale analysis of disease mutations and interactors.

Minervini G, Quaglia F, Tabaro F, Tosatto S PLoS Comput Biol. 2019; 15(4):e1006478.

PMID: 30943211 PMC: 6464237. DOI: 10.1371/journal.pcbi.1006478.

Chaperone-E3 Ligase Complex HSP70-CHIP Mediates Ubiquitination of Ribosomal Protein S3.

Hwang I, Cho S, Ahn J Int J Mol Sci. 2018; 19(9).

PMID: 30213050 PMC: 6163665. DOI: 10.3390/ijms19092723.

Plasma proteomic study of acute mountain sickness susceptible and resistant individuals.

Lu H, Wang R, Li W, Xie H, Wang C, Hao Y Sci Rep. 2018; 8(1):1265.

PMID: 29352170 PMC: 5775437. DOI: 10.1038/s41598-018-19818-9.

Knockdown of IRE1α inhibits colonic tumorigenesis through decreasing β-catenin and IRE1α targeting suppresses colon cancer cells.

Li X, Zhang H, Xu Y, Zhang R, Chen Y, Fan L Oncogene. 2017; 36(48):6738-6746.

PMID: 28825721 DOI: 10.1038/onc.2017.284.

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