pVHL mediates K63-linked ubiquitination of nCLU

pVHL, product of von Hippel-Lindau (VHL) tumor suppressor gene, functions as the substrate recognition component of an E3-ubiquitin ligase that targets proteins for ubiquitination and proteasomal degradation. Hypoxia-inducible factor α (HIFα) is the well-known substrate of pVHL. Besides HIFα, pVHL a...

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Bibliographic Details
Published in:PloS one 2012-04, Vol.7 (4), p.e35848-e35848
Main Authors: Xue, Jing, Lv, Dan-Dan, Jiao, Shi, Zhao, Wenting, Li, Xuebing, Sun, Heng, Yan, Bing, Fan, Li, Hu, Rong-Gui, Fang, Jing
Format: Article
Language:English
Subjects:
Apoptosis
Biology
Cell Nucleus - genetics
Cell Nucleus - metabolism
Cloning
Clusterin
Clusterin - genetics
Clusterin - metabolism
Colorectal cancer
Cysts
Gene expression
HEK293 Cells
Humans
Hypoxia
Hypoxia-Inducible Factor 1, alpha Subunit - genetics
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Hypoxia-inducible factors
Kinases
Laboratories
Ligases
Medicine
Metabolism
Neoplasia
Nuclear transport
Nutrition
Penicillin
Phosphatase
Prostate cancer
Proteasome Endopeptidase Complex - genetics
Proteasome Endopeptidase Complex - metabolism
Proteasomes
Protein binding
Proteins
Recognition
RNA polymerase
Translocation
Tumor suppressor genes
Tumors
Ubiquitin
Ubiquitin-protein ligase
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
Ubiquitination
Ubiquitination - physiology
VHL protein
Von Hippel-Lindau Tumor Suppressor Protein - genetics
Von Hippel-Lindau Tumor Suppressor Protein - metabolism
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Summary:pVHL, product of von Hippel-Lindau (VHL) tumor suppressor gene, functions as the substrate recognition component of an E3-ubiquitin ligase that targets proteins for ubiquitination and proteasomal degradation. Hypoxia-inducible factor α (HIFα) is the well-known substrate of pVHL. Besides HIFα, pVHL also binds to many other proteins and has multiple functions. In this manuscript, we report that the nuclear clusterin (nCLU) is a target of pVHL. We found that pVHL had a direct interaction with nCLU. nCLU bound to pVHL at pVHL's β domain, the site for recognition of substrate, indicating that nCLU might be a substrate of pVHL. Interestingly, pVHL bound to nCLU but did not lead to nCLU destruction. Further studies indicated that pVHL mediated K63-linked ubiquitination of nCLU and promoted nCLU nuclear translocation. In summary, our results disclose a novel function of pVHL that mediates K63-linked ubiquitination and identify nCLU as a new target of pVHL.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0035848