Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P43146 (
tumour suppressor
)
5,935
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Von Hippel-Lindau disease (VHL) is caused by germline mutations in the VHL
tumour suppressor
gene. Tumour development in this setting is due to loss or inactivation of the remaining wild-type VHL allele. The VHL gene product (pVHL) resides primarily in the cytoplasm. A frequently mutated region of pVHL can bind to complexes containing elongin B,
elongin C
and Cul2. Loss of pVHL leads to an inappropriate accumulation of hypoxia-inducible mRNAs, such as the mRNA encoding vascular endothelial growth factor (VEGF), under normoxic conditions. This finding is most likely to account for the hypervascular nature of VHL-associated neoplasms. Current studies are focussed on understanding if and how binding to elongins and Cul2 is linked to the ability of pVHL to regulate hypoxia-inducible mRNAs. In this regard, it is perhaps noteworthy that
elongin C
and Cul2 are homologous to yeast proteins Skp1 and Cdc53. These latter proteins participate in the formation of complexes that target certain proteins for ubiquitination.
...
PMID:Functions of the von Hippel-Lindau tumour suppressor protein. 968 55
von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by germline mutations of the VHL
tumour suppressor
gene. The VHL gene product, pVHL, forms multiprotein complexes that contain elongin B,
elongin C
and Cul-2, and negatively regulates hypoxia-inducible mRNAs. pVHL is suspected to play a role in ubiquitination given the similarity of
elongin C
and Cul-2 with Skp1 and Cdc53, respectively. pVHL can also interact with fibronectin and is required for the assembly of a fibronectin matrix. Finally, pVHL, at least indirectly, plays a role in the ability of cells to exit the cell cycle. Thus, pVHL is a
tumour suppressor
protein that regulates angiogenesis, extracellular matrix formation and the cell cycle.
...
PMID:The von Hippel-Lindau tumour suppressor protein: new perspectives. 1036 21
