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  • Title: von Hippel-Lindau tumor suppressor: not only HIF's executioner.
    Author: Czyzyk-Krzeska MF, Meller J.
    Journal: Trends Mol Med; 2004 Apr; 10(4):146-9. PubMed ID: 15162797.
    Abstract:
    Loss of von Hippel-Lindau (VHL) protein function results in an autosomal-dominant cancer syndrome known as VHL disease, which manifests as angiomas of the retina, hemangioblastomas of the central nervous system, renal clear-cell carcinomas and pheochromocytomas. VHL tumor suppressor is a specific substrate-recognition component of the E3 ubiquitin complex, which regulates proteasomal degradation of the subunit of the hypoxia inducible transcription factor (HIF). Impaired VHL complex function leads to accumulation of HIF, overexpression of various HIF-induced gene products and formation of highly vascular neoplasia. However, the ubiquitylating role of the VHL complex extends beyond its function in regulating HIF, as it appears to regulate the stability of other proteins that might be involved in various steps of oncogenic processes.
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