Von Hippel Lindau

Staller P, Sulitkova J, Lisztwan J, Moch H, Oakeley EJ, Krek W (2003) Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL. Nature 425 307-311... 

Zagzag D, Krishnamachary B, Yee H, et al. Stromal cell-derived factor-la and CXCR4 expression in hemangioblastoma and clear cell-renal cell carcinoma von Hippel-Lindau loss-of-function induces expression of a ligand and its receptor. Cancer Res 2005 65 6178-6188. 

Pause, A., et al.. The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins. Proc Natl Acad Sci USA, 1997, 94(6), 2156-61. 

Ohh, M., et al., Ubiquitination of hypoxia-indudble factor requires direct binding to the -domain of the von Hippel-Lindau protein. Nat Cell Biol, 2000, 2(7), 423-7. 

Latif, F. et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 1993, 260, 1317-20. 

Loneegan, K. M. et al. Regulation of hypoxia-inducible mRNAs by the von Hippel-Lindau tumor suppressor protein requires binding to complexes containing elongins B/C and Cul2. 

Ivan, M. and Kaelin, W. G., Jr. The von Hippel-Lindau tumor suppressor protein. Curr Opin Genet Dev 2001, 3 3, 27-34. 

Jaakkoia, P. et al. Targeting of HlFalpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 2001, 292, 468-72. 

Ubiquitination of a novel deubiq-uitinating enzyme requires direct binding to von Hippel-Lindau tumor suppressor protein, J Biol Chem,... 

Coen, P. G., McDonald, E. R., 3rd, Herman, J. G., and El-Deiey, W. S. Tat-binding protein-1, a component of the 26 S proteasome, contributes to the E3 ubiquitin ligase function of the von Hippel-Lindau protein. Nat Genet... 

E3 iigase Von Hippel-Lindau (VHL) disease Mutation in the VHL protein 409 ... 

Recent studies have demonstrated that overexpression of HDACl represses the tumor suppressors, p53 and von Hippel-Lindau (VHL), but induces the hypoxia-responsive genes, hypoxia inducible factor alpha (HIF-la) and vascular endothelial growth factor (VEGF) and increases angiogenesis. Conversely, HDAC inhibitors derepress the tumor suppressors, p53 and VHL, and repress HIF-la and VEGF [68, 69]. 

Jaakkola P, Mole DR, Han YM, Wilson MI, Gielbert J, Gaskell SJ, Kriegsheim AV, Hebestreit HF, Mukherji M, Schofield CJ, Maxwell PH, Pugh CW, Ratcliffe PJ (2001) Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by (Deregulated prolyl hydroxylation. Science 292(5516) 468 172... 

According to the Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC), RCC can be histopafhologically classified into the most prominent clear cell type, which is associated with the occurrence of highly specific deletion of chromosome 3p and mutation of the von Hippel Lindau VHL) gene as well as the chromophobe, papillary/chromophil or collecting duct types (Kovacs, 1999). 

Recent comparison of gene expression profiles of von Hippel-lindau-i- versus von Hippel-lindau-ceU lines obtained from the clear cell RCC subtype identified proteins that might serve as candidate molecular markers. Inactivation of VHL is a hallmark in most sporadic clear cell RCC and it occurs early in renal carcinogenesis (Skates and Iliopoulus., 2004 Latifet al, 1993). Furthermore, the profile of secreted proteins could be directly AQ4 determined by analyzing comparatively the genomic and proteomic patterns of these cell lines as well as their conditioned tissue culture supernatants (Ferguson et al, 2004). A combination of cDNA microarray and proteome analyses appears reasonable since not every difference at the transcriptome level will translate into differences at the protein level, whereas posttranscriptional/posttranslational modifications were not detectable by tran-scriptomics. 

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