PUBLICATION
Complex cellular functions of the von Hippel-Lindau tumor suppressor gene: insights from model organisms
- Authors
- Hsu, T.
- ID
- ZDB-PUB-111027-7
- Date
- 2012
- Source
- Oncogene 31(18): 2247-2257 (Review)
- Registered Authors
- Hsu, Todd
- Keywords
- none
- MeSH Terms
-
- Animals
- Caenorhabditis elegans
- Drosophila
- Gene Expression Regulation*
- Hematopoiesis/genetics
- Hypoxia-Inducible Factor 1, alpha Subunit/genetics
- Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
- Inflammation/genetics
- Mice
- Models, Animal*
- Morphogenesis/genetics
- Neoplasms/genetics
- Neoplasms/metabolism
- Neoplasms/pathology
- Oxygen/metabolism
- Von Hippel-Lindau Tumor Suppressor Protein/genetics*
- Von Hippel-Lindau Tumor Suppressor Protein/metabolism
- Zebrafish
- PubMed
- 21996733 Full text @ Oncogene
Citation
Hsu, T. (2012) Complex cellular functions of the von Hippel-Lindau tumor suppressor gene: insights from model organisms. Oncogene. 31(18):2247-2257.
Abstract
The von Hippel–Lindau tumor suppressor gene (VHL) has attracted intensive interest not only because its mutations predispose carriers to devastating tumors, but also because it is involved in oxygen sensing under physiological conditions. VHL loss-of-function mutations result in organ-specific tumors, such as hemangioblastoma of the central nervous system and renal cell carcinoma, both untreatable with conventional chemotherapies. The VHL protein is best known as an E3 ubiquitin ligase that targets hypoxia-inducible factor-α (HIF-α), but many diverse, non-canonical cellular functions have also been assigned to VHL, mainly based on studies in cell culture systems. As such, although the HIF-dependent role of VHL is critical, the full spectrum of pathophysiological functions of VHL is still unresolved. Such understanding requires careful cross-referencing with physiologically relevant experimental models. Studies in model systems, such as Caenorhabditis elegans, Drosophila, zebrafish and mouse have provided critical in vivo confirmation of the VHL–HIF pathway, and verification of potentially important cellular functions including microtubule stabilization and epithelial morphogenesis. More recently, animal models have also suggested systemic roles of VHL in hematopoiesis, metabolic homeostasis and inflammation. In this review, the studies performed in model organisms will be summarized and placed in context with existing clinical and in vitro data.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping