title: The VHL short variant involves in protein quality control.
abstract: The von Hippel-Lindau (VHL) is the most important and frequently mutated gene in human clear cell renal cell carcinoma (ccRCC). In contrast to its long counterpart, the internal translational variant of VHL protein (VHLs) is evolutionarily conserved. Herein we present evidence that VHLs associates with ribosome complex via interaction with the large subunit 6 (RPL6). Manipulation of VHLs expression significantly alters protein synthesis, cell size and mitochondrial mass. VHLs deficiency leads to remarkable sensitivity to drug treatments eliciting nascent protein mis-folding and translational errors. The ubiquitination of nascent peptides are dramatically increased upon the ectopic over-expression of VHLs, which simultaneously co-localizes with proteasome and thus may facilitate the ubiquitin-proteasome mediated degradation. In summary, VHLs contributes to protein quality control in addition to its canonical function in maintaining homeostasis of hypoxia-induced factors alpha subunit (HIFα) in response to environmental oxygen supply.
authors.affiliation: Collaborative Innovation Center of Cancer Medicine, National Institute of Biological Sciences, Beijing, Beijing 102206, China. Electronic address: yanbliu2012@sina.cn.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing 102206, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Yang
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing 102206, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Zuo
authors.affiliation: Collaborative Innovation Center of Cancer Medicine, National Institute of Biological Sciences, Beijing, Beijing 102206, China. Electronic address: chengliang@nibs.ac.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
mesh_terms: D002470:Cell Survival; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014176:Protein Biosynthesis; D059748:Proteolysis; D054683:Ribosome Subunits, Large, Eukaryotic / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D054875:Ubiquitination; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D046988:Proteasome Endopeptidase Complex; C497446:VHL protein, human
keywords: Proteasome; Protein quality control; Ribosome; Ubiquitination; VHL