pVHL mediates K63-linked ubiquitination of nCLU

• Published in: PloS one Vol. 7; no. 4; p. 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: Journal Article
• Language: English
• Published: United States Public Library of Science 20.04.2012; Public Library of Science (PLoS)
• 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; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0035848

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.