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  • Title: Drosophila von Hippel-Lindau tumor suppressor complex possesses E3 ubiquitin ligase activity.
    Author: Aso T, Yamazaki K, Aigaki T, Kitajima S.
    Journal: Biochem Biophys Res Commun; 2000 Sep 16; 276(1):355-61. PubMed ID: 11006129.
    Abstract:
    Mutations of the von Hippel-Lindau (VHL) tumor suppressor gene predispose individuals to a variety of human tumors, including renal cell carcinoma, hemangioblastoma of the central nervous system, and pheochromocytoma. Here we report on the identification and characterization of the Drosophila homolog of VHL. The predicted amino acid sequence of Drosophila VHL protein shows 29% identity and 44% similarity to that of human VHL protein. Biochemical studies have shown that Drosophila VHL protein binds to Elongins B and C directly, and via this Elongin BC complex, associates with Cul-2 and Rbx1. Like human VHL, Drosophila VHL complex containing Cul-2, Rbx1, Elongins B and C, exhibits E3 ubiquitin ligase activity. In addition, we provide evidence that hypoxia-inducible factor (HIF)-1alpha is the ubiquitination target of both human and Drosophila VHL complexes.
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