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PLoS One. 2012;7(4):e35848. doi: 10.1371/journal.pone.0035848. Epub 2012 Apr 20.

pVHL mediates K63-linked ubiquitination of nCLU.

Author information

1
The Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences, Shanghai, China.

Abstract

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.

PMID:
22532874
PMCID:
PMC3332038
DOI:
10.1371/journal.pone.0035848
[Indexed for MEDLINE]
Free PMC Article

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