von Hippel-Lindau tumor suppressor: not only HIF's executioner.
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.
Czyzyk-Krzeska
Maria F
MF
Department of Genome Science, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0505, USA. Maria.Czyzykkrzeska@uc.edu
Meller
Jaroslaw
J
D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006391:Hemangioma / Q000473:pathology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism / Q000502:physiology*; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000235:genetics / Q000473:pathology
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D012319:RNA Polymerase II; C497446:VHL protein, human