Biomaterial Database

Beyond the hypoxia-inducible factor-centric tumour suppressor model of von Hippel-Lindau. 2008

Andrew M Roberts, and Michael Ohh

Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada.

OBJECTIVE To provide an overview of the recent advances in the understanding of the molecular mechanisms governing the tumour suppressor functions of the von Hippel-Lindau protein. RESULTS von Hippel-Lindau is a vital component of an E3 ubiquitin ligase complex involved in the oxygen-dependent targeting of hypoxia-inducible factor for ubiquitin-mediated destruction. Recent reports have linked von Hippel-Lindau to the regulation of diverse biological processes including cell adhesion, extracellular matrix assembly and ciliogenesis in a manner dependent and/or independent of hypoxia-inducible factor. CONCLUSIONS The tumour suppressor function of von Hippel-Lindau has remained hypoxia-inducible factor-centric since the discovery of von Hippel-Lindau as a bona fide negative regulator of the ubiquitous oxygen-sensing pathway. Emerging evidence supports this hypothesis with the elucidation of fundamental cellular processes deregulated upon the inactivation of the von Hippel-Lindau-hypoxia-inducible factor pathway, but has also proved compelling on the hypoxia-inducible factor-independent tumour suppressor role of von Hippel-Lindau. These and continuing studies into the molecular pathways and mechanisms governing the tumour suppressor functions of von Hippel-Lindau will ultimately afford new avenues for anticancer strategies for the improved treatment of a diverse array of cancers.

UI	MeSH Term	Description	Entries
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D005109	Extracellular Matrix	A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.	Matrix, Extracellular,Extracellular Matrices,Matrices, Extracellular
D006623	von Hippel-Lindau Disease	An autosomal dominant disorder caused by mutations in a tumor suppressor gene. This syndrome is characterized by abnormal growth of small blood vessels leading to a host of neoplasms. They include HEMANGIOBLASTOMA in the RETINA; CEREBELLUM; and SPINAL CORD; PHEOCHROMOCYTOMA; pancreatic tumors; and renal cell carcinoma (see CARCINOMA, RENAL CELL). Common clinical signs include HYPERTENSION and neurological dysfunctions.	Cerebelloretinal Angiomatosis, Familial,Lindau Disease,Angiomatosis Retinae,Familial Cerebello-Retinal Angiomatosis,Hippel-Lindau Disease,Lindau's Disease,VHL Syndrome,von Hippel-Lindau Syndrome,Angiomatoses, Familial Cerebello-Retinal,Angiomatoses, Familial Cerebelloretinal,Angiomatosis, Familial Cerebello-Retinal,Angiomatosis, Familial Cerebelloretinal,Cerebello-Retinal Angiomatoses, Familial,Cerebello-Retinal Angiomatosis, Familial,Cerebelloretinal Angiomatoses, Familial,Familial Cerebello Retinal Angiomatosis,Familial Cerebello-Retinal Angiomatoses,Familial Cerebelloretinal Angiomatoses,Familial Cerebelloretinal Angiomatosis,Hippel Lindau Disease,Lindau's Diseases,Lindaus Disease,VHL Syndromes,von Hippel Lindau Disease,von Hippel Lindau Syndrome
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015820	Cadherins	Calcium-dependent cell adhesion proteins. They are important in the formation of ADHERENS JUNCTIONS between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (E- for epithelial, N- for neural, and P- for placental cadherins) or by numbers (cadherin-12 or N-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body.	Cadherin,E-Cadherins,Epithelial-Cadherin,Liver Cell Adhesion Molecules,N-Cadherins,Neural Cadherin,P-Cadherins,Uvomorulin,Cadherin-1,Cadherin-2,Cadherin-3,E-Cadherin,Epithelial-Cadherins,Liver Cell Adhesion Molecule,N-Cadherin,Neural Cadherins,P-Cadherin,Placental Cadherins,Cadherin 1,Cadherin 2,Cadherin 3,Cadherin, Neural,Cadherins, Neural,Cadherins, Placental,E Cadherin,E Cadherins,Epithelial Cadherin,Epithelial Cadherins,N Cadherin,N Cadherins,P Cadherin,P Cadherins
D051177	Catenins	A family of cytoskeletal proteins that play essential roles in CELL ADHESION at ADHERENS JUNCTIONS by linking CADHERINS to the ACTIN FILAMENTS of the CYTOSKELETON.	Catenin,Catenin Protein,Catenin Proteins,Protein, Catenin
D051793	Hypoxia-Inducible Factor 1	A basic helix-loop-helix transcription factor that plays a role in APOPTOSIS. It is composed of two subunits: ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR and HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT.	Hypoxia Inducible Factor 1
D051794	Von Hippel-Lindau Tumor Suppressor Protein	A ubiquitin-protein ligase that mediates OXYGEN-dependent polyubiquitination of HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT. It is inactivated in VON HIPPEL-LINDAU SYNDROME.	VHL Tumor Suppressor Protein,Von Hippel Lindau Tumor Suppressor Protein