| Von Hippel-Lindau Syndrome (VHL) is a rare genetic disorder, which causes the growth of tumors in specific tissues of the body. VHL is part of an E3 ubiquitin ligase complex that targets the transcription factor HIF-alpha for polyubiquitination and proteasomal degradation. VHL has also been shown to play significant roles in cellular phenotypes including morphology, cellular differentiation, integrin levels, fibronectin deposition, and cell cycling. We investigated the role of HIF-alpha regulation in these phenotypes in renal carcinoma cells. Results suggest that HIF2-alpha regulation may play a partial role in the cellular morphological phenotype and in regulation of integrin expression. In contrast, HIF2-alpha played no role in regulation of fibronectin matrix assembly, cell cycle regulation, and renal cell differentiation in the A498 cell line. The later phenotypes are apparently solely dependent on the VHL protein. These results suggest that pVHL may have other important biochemical functions in addition to HIF-alpha regulation. |
