title: pVHL mediates K63-linked ubiquitination of nCLU.
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.
authors.affiliation: The Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Lv
authors.forename: Shi
authors.initials: S
authors.lastname: Jiao
authors.forename: Wenting
authors.initials: W
authors.lastname: Zhao
authors.forename: Xuebing
authors.initials: X
authors.lastname: Li
authors.forename: Heng
authors.initials: H
authors.lastname: Sun
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.forename: Li
authors.initials: L
authors.lastname: Fan
authors.forename: Rong-Gui
authors.initials: RG
authors.lastname: Hu
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
mesh_terms: D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D051152:Clusterin / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051152:Clusterin; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D046988:Proteasome Endopeptidase Complex; C497446:VHL protein, human