Hypoxia-inducible factor linked to differential kidney cancer risk seen with type 2A and type 2B VHL mutations

Molecular and Cellular Biology

Volumn 27, Issue 15, 2007, Pages 5381-5392

  Li, Lianjie ^a,b   Zhang, Liang ^c   Zhang, Xiaoping ^c   Yan, Qin ^a,b   Minamishima, Yoji Andrew ^a   Olumi, Aria F ^c   Mao, Mao ^d   Bartz, Steven ^d   Kaelin Jr , William G ^a,b,e  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d ROSETTA INPHARMATICS   (United States)

^e DANA FARBER CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HYPOXIA INDUCIBLE FACTOR 2ALPHA; VON HIPPEL LINDAU PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER MODEL; CANCER RISK; CLEAR CELL CARCINOMA; DNA METHYLATION; HUMAN; HUMAN CELL; KIDNEY CANCER; MISSENSE MUTATION; MOUSE; NONHUMAN; NUDE MOUSE; PRIORITY JOURNAL; PROTEIN ENGINEERING; PROTEIN FUNCTION; RISK ASSESSMENT; TUMOR GROWTH; TUMOR SUPPRESSOR GENE; TUMOR XENOGRAFT; VHL GENE;

ANIMALS; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CARCINOMA, RENAL CELL; CELL CYCLE; CELL LINE, TUMOR; CELL PROLIFERATION; DOWN-REGULATION; GENE EXPRESSION PROFILING; HUMANS; KIDNEY NEOPLASMS; MICE; MUTANT PROTEINS; MUTATION; RISK FACTORS; SPHEROIDS, CELLULAR; VON HIPPEL-LINDAU TUMOR SUPPRESSOR PROTEIN;

EID: 34547174217     PISSN: 02707306     EISSN: None     Source Type: Journal    
DOI: 10.1128/MCB.00282-07     Document Type: Article

References (79)

1. An, Z., P. Jiang, X. Wang, A. R. Moossa, and R. M. Hoffman. 1999. Development of a high metastatic orthotopic model of human renal cell carcinoma in nude mice: benefits of fragment implantation compared to cell-suspension injection. Clin. Exp. Metastasis 17:265-270.
2. Appelhoff, R. J., Y. M. Tian, R. R. Raval, H. Turley, A. L. Harris, C. W. Pugh, P. J. Ratcliffe, and J. M. Gleadle. 2004. Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor. J. Biol. Chem. 279:38458-38465.
3. Aprelikova, O., G. V. Chandramouli, M. Wood, J. R. Vasselli, J. Riss, J. K. Maranchie, W. M. Linehan, and J. C. Barrett. 2004. Regulation of HIF prolyl hydroxylases by hypoxia-inducible factors. J. Cell Biochem. 92:491-501.
4. Benjamin, L. E., and E. Keshet. 1997. Conditional switching of vascular endothelial growth factor (VEGF) expression in tumors: induction of endothelial cell shedding and regression of hemangioblastoma-like vessels by VEGF withdrawal. Proc. Natl. Acad. Sci. USA 94:8761-8766.
5. Bruick, R. K., and S. L. McKnight. 2001. A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294:1337-1340.
6. Chen, F., T. Kishida, M. Yao, T. Hustad, D. Glavac, M. Dean, J. R. Gnarra, M. L. Orcutt, F. M. Duh, G. Glenn, et al. 1995. Germline mutations in the von Hippel-Lindau disease tumor suppressor gene: correlations with phenotype. Hum. Mutat. 5:66-75.
7. Clifford, S. C., M. E. Cockman, A. C. Smallwood, D. R. Mole, E. R. Woodward, P. H. Maxwell, P. J. Ratcliffe, and E. R. Maher. 2001. Contrasting effects on HIF-1alpha regulation by disease-causing pVHL mutations correlate with patterns of tumourigenesis in von Hippel-Lindau disease. Hum. Mol. Genet. 10:1029-1038.
8. Cohen, H. T., and F. J. McGovern. 2005. Renal-cell carcinoma. N. Engl. J. Med. 353:2477-2490.
9. Crossey, P. A., F. M. Richards, K. Foster, J. S. Green, A. Prowse, F. Latif, M. I. Lerman, B. Zbar, N. A. Affara, M. A. Ferguson-Smith, et al. 1994. Identification of intragenic mutations in the von Hippel-Lindau disease tumour suppressor gene and correlation with disease phenotype. Hum. Mol. Genet. 3:1303-1308.
10. Czyzyk-Krzeska, M. F., and J. Meller. 2004. von Hippel-Lindau tumor suppressor: not only HIF's executioner. Trends Mol. Med. 10:146-149.
11. Dahia, P. L., K. N. Ross, M. E. Wright, C. Y. Hayashida, S. Santagata, M. Barontini, A. L. Kung, G. Sanso, J. F. Powers, A. S. Tischler, R. Hodin, S. Heitritter, F. Moore, R. Dluhy, J. A. Sosa, I. T. Ocal, D. E. Benn, D. J. Marsh, B. G. Robinson, K. Schneider, J. Garber, S. M. Arum, M. Korbonits, A. Grossman, P. Pigny, S. P. Toledo, V. Nose, C. Li, and C. D. Stiles. 2005. A HIF1α regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas. PLOS Genet. 1:72-80.
12. Davidowitz, E. J., A. R. Schoenfeld, and R. D. Burk. 2001. VHL induces renal cell differentiation and growth arrest through integration of cell-cell and cell-extracellular matrix signaling. Mol. Cell. Biol. 21:865-874.
13. del Peso, L., M. C. Castellanos, E. Temes, S. Martin-Puig, Y. Cuevas, G. Olmos, and M. O. Landazuri. 2003. The von Hippel Lindau/hypoxia-inducible factor (HIF) pathway regulates the transcription of the HIF-proline hydroxylase genes in response to low oxygen. J. Biol. Chem. 278:48690-48695.
14. de Paulsen, N., A. Brychzy, M. C. Fournier, R. D. Klausner, J. R. Gnarra, A. Pause, and S. Lee. 2001. Role of transforming growth factor-alpha in von Hippel-Lindau (VHL) (-/-) clear cell renal carcinoma cell proliferation: a possible mechanism coupling VHL tumor suppressor inactivation and tumorigenesis. Proc. Natl. Acad. Sci. USA 98:1387-1392.
15. Duan, D. R., J. S. Humphrey, D. Y. Chen, Y. Weng, J. Sukegawa, S. Lee, J. R. Gnarra, W. M. Linehan, and R. D. Klausner. 1995. Characterization of the VHL tumor suppressor gene product: localization, complex formation, and the effect of natural inactivating mutations. Proc. Natl. Acad. Sci. USA 92:6459-6463.
16. Duan, D. R., A. Pause, W. H. Burgess, T. Aso, D. Y. Chen, K. P. Garrett, R. C. Conaway, J. W. Conaway, W. M. Linehan, and R. D. Klausner. 1995. Inhibition of transcription elongation by the VHL tumor suppressor protein. Science 269:1402-1406.
17. Epstein, A. C., J. M. Gleadle, L. A. McNeill, K. S. Hewitson, J. O'Rourke, D. R. Mole, M. Mukherji, E. Metzen, M. I. Wilson, A. Dhanda, Y. M. Tian, N. Masson, D. L. Hamilton, P. Jaakkola, R. Barstead, J. Hodgkin, P. H. Maxwell, C. W. Pugh, C. J. Schofield, and P. J. Ratcliffe. 2001. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107:43-54.
18. Esteban, M. A., M. G. Tran, S. K. Harten, P. Hill, M. C. Castellanos, A. Chandra, R. Raval, T. S. O'Brien, and P. H. Maxwell. 2006. Regulation of E-cadherin expression by VHL and hypoxia-inducible factor. Cancer Res. 66:3567-3575.
19. Evans, A. J., R. C. Russell, O. Roche, T. N. Burry, J. E. Fish, V. W. Chow, W. Y. Kim, A. Saravanan, M. A. Maynard, M. L. Gervais, R. I. Sufan, A. M. Roberts, L. A. Wilson, M. Betten, C. Vandewalle, G. Berx, P. A. Marsden, M. S. Irwin, B. T. Teh, M. A. Jewett, and M. Ohh. 2007. VHL Promotes E2 box-dependent E-cadherin transcription by HIF-mediated regulation of SIP1 and Snail. Mol. Cell. Biol. 27:157-169.
20. Fidler, I. J., S. Naito, and S. Pathak. 1990. Orthotopic implantation is essential for the selection, growth and metastasis of human renal cell cancer in nude mice. Cancer Metastasis Rev. 9:149-165. (Erratum, 10:79, 1991.)
21. Gnarra, J. R., S. Zhou, M. J. Merrill, J. R. Wagner, A. Krumm, E. Papavassiliou, E. H. Oldfield, R. D. Klausner, and W. M. Linehan. 1996. Post-transcriptional regulation of vascular endothelial growth factor mRNA by the product of the VHL tumor suppressor gene. Proc. Natl. Acad. Sci. USA 93:10589-10594.
22. Gunaratnam, L., M. Morley, A. Franovic, N. de Paulsen, K. Mekhail, D. A. Parolin, E. Nakamura, I. A. Lorimer, and S. Lee. 2003. Hypoxia inducible factor activates the transforming growth factor-alpha/epidermal growth factor receptor growth stimulatory pathway in VHL(-/-) renal cell carcinoma cells. J. Biol. Chem. 278:44966-44974.
23. Haase, V. H., J. N. Glickman, M. Socolovsky, and R. Jaenisch. 2001. Vascular tumors in livers with targeted inactivation of the von Hippel-Lindau tumor suppressor. Proc. Natl. Acad. Sci. USA 98:1583-1588.
24. Harris, A. L. 2002. Hypoxia - a key regulatory factor in tumour growth. Nat. Rev. Cancer 2:38-47.
25. Hergovich, A., J. Lisztwan, R. Barry, P. Ballschmieter, and W. Krek. 2003. Regulation of microtubule stability by the von Hippel-Lindau tumour suppressor protein pVHL. Nat. Cell Biol. 5:64-70.
26. Hoffman, M. A., M. Ohh, H. Yang, J. M. Klco, M. Ivan, and W. G. Kaelin, Jr. 2001. von Hippel-Lindau protein mutants linked to type 2C VHL disease preserve the ability to downregulate HIF. Hum. Mol. Genet. 10:1019-1027.
27. Hon, W. C., M. I. Wilson, K. Harlos, T. D. Claridge, C. J. Schofield, C. W. Pugh, P. H. Maxwell, P. J. Ratcliffe, D. I. Stuart, and E. Y. Jones. 2002. Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHL. Nature 417:975-978.
28. Hudes, G., M. Carducci, J. Tomczak, J. Dutcher, R. Figlin, A. Kapoor, E. Staroslawska, T. O'Toole, Y. Park, and L. Moore. 2006. A phase 3, randomized, 3-arm study of temsirolimus (TEMSR) or interferon-alpha (IFN) or the combination of TEMSR + IFN in the treatment of first-line, poor-risk patients with advanced renal cell carcinoma (adv RCC), abstr. LBA4. In 2006 ASCO annual meetings proceedings, part I. J. Clin. Oncol. 24:18S.
29. Hughes, T. R., M. Mao, A. R. Jones, J. Burchard, M. J. Marton, K. W. Shannon, S. M. Lefkowitz, M. Ziman, J. M. Schelter, M. R. Meyer, S. Kobayashi, C. Davis, H. Dai, Y. D. He, S. B. Stephaniants, G. Cavet, W. L. Walker, A. West, E. Coffey, D. D. Shoemaker, R. Stoughton, A. P. Blanchard, S. H. Friend, and P. S. Linsley. 2001. Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer. Nat. Biotechnol. 19:342-347.
30. Iliopoulos, O., A. Kibel, S. Gray, and W. G. Kaelin, Jr. 1995. Tumour suppression by the human von Hippel-Lindau gene product. Nat. Med. 1:822-826.
31. Ivan, M., T. Haberberger, D. C. Gervasi, K. S. Michelson, V. Gunzler, K. Kondo, H. Yang, I. Sorokina, R. C. Conaway, J. W. Conaway, and W. G. Kaelin, Jr. 2002. Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor. Proc. Natl. Acad. Sci. USA 99:13459-13464.
32. Ivan, M., K. Kondo, H. Yang, W. Kim, J. Valiando, M. Ohh, A. Salic, J. M. Asara, W. S. Lane, and W. G. Kaelin, Jr. 2001. HIFα targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292:464-468.
33. Iwai, K., K. Yamanaka, T. Kamura, N. Minato, R. C. Conaway, J. W. Conaway, R. D. Klausner, and A. Pause. 1999. Identification of the von Hippel-Lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex. Proc. Natl. Acad. Sci. USA 96:12436-12441.
34. Jaakkola, P., D. R. Mole, Y. M. Tian, M. I. Wilson, J. Gielbert, S. J. Gaskell, A. Kriegsheim, H. F. Hebestreit, M. Mukherji, C. J. Schofield, P. H. Maxwell, C. W. Pugh, and P. J. Ratcliffe. 2001. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292:468-472.
35. Kaelin, W. G. 2005. Proline hydroxylation and gene expression. Annu. Rev. Biochem. 74:115-128.
36. Kaelin, W. G., Jr. 2002. Molecular basis of the VHL hereditary cancer syndrome. Nat. Rev. Cancer 2:673-682.
37. Kaelin, W. G., Jr. 2005. The von Hippel-Lindau protein, HIF hydroxylation, and oxygen sensing. Biochem. Biophys. Res. Commun. 338:627-638.
38. Kaelin, W. G., Jr. 2004. The von Hippel-Lindau tumor suppressor gene and kidney cancer. Clin. Cancer Res. 10:6290S-6295S.
39. Kamura, T., M. N. Conrad, Q. Yan, R. C. Conaway, and J. W. Conaway. 1999. The Rbx1 subunit of SCF and VHL E3 ubiquitin ligase activates Rub1 modification of cullins Cdc53 and Cul2. Genes Dev. 13:2928-2933.
40. Kamura, T., D. M. Koepp, M. N. Conrad, D. Skowyra, R. J. Moreland, O. Iliopoulos, W. S. Lane, W. G. Kaelin, Jr., S. J. Elledge, R. C. Conaway, J. W. Harper, and J. W. Conaway. 1999. Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase. Science 284:657-661.
41. Kamura, T., K. Maenaka, S. Kotoshiba, M. Matsumoto, D. Kohda, R. C. Conaway, J. W. Conaway, and K. I. Nakayama. 2004. VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases. Genes Dev. 18:3055-3065.
42. Kibel, A., O. Iliopoulos, J. A. DeCaprio, and W. G. Kaelin, Jr. 1995. Binding of the von Hippel-Lindau tumor suppressor protein to elongin B and C. Science 269:1444-1446.
43. Kim, W. Y., and W. G. Kaelin. 2004. Role of VHL gene mutation in human cancer. J. Clin. Oncol. 22:4991-5004.
44. Kim, W. Y., M. Safran, M. R. Buckley, B. L. Ebert, J. Glickman, M. Bosenberg, M. Regan, and W. G. Kaelin, Jr. 2006. Failure to prolyl hydroxylate hypoxia-inducible factor alpha phenocopies VHL inactivation in vivo. EMBO J. 25:4650-4662.
45. Kishida, T., T. M. Stackhouse, F. Chen, M. I. Lerman, and B. Zbar. 1995. Cellular proteins that bind the von Hippel-Lindau disease gene product: mapping of binding domains and the effect of missense mutations. Cancer Res. 55:4544-4548.
46. Knauth, K., C. Bex, P. Jemth, and A. Buchberger. 2006. Renal cell carcinoma risk in type 2 von Hippel-Lindau disease correlates with defects in pVHL stability and HIF-1α interactions. Oncogene 25:370-377.
47. Kondo, K., W. Y. Kim, M. Lechpammer, and W. G. Kaelin, Jr. 2003. Inhibition of HIF2α is sufficient to suppress pVHL-defective tumor growth. PLOS Biol. 1:E83.
48. Kondo, K., J. Klco, E. Nakamura, M. Lechpammer, and W. G. Kaelin, Jr. 2002. Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. Cancer Cell 1:237-246.
49. Krishnamachary, B., D. Zagzag, H. Nagasawa, K. Rainey, H. Okuyama, J. H. Baek, and G. L. Semenza. 2006. Hypoxia-inducible factor-1-dependent repression of E-cadherin in von Hippel-Lindau tumor suppressor-null renal cell carcinoma mediated by TCF3, ZFHX1A, and ZFHX1B. Cancer Res. 66:2725-2731.
50. Lee, S., E. Nakamura, H. Yang, W. Wei, M. S. Linggi, M. P. Sajan, R. V. Farese, R. S. Freeman, B. D. Carter, W. G. Kaelin, Jr., and S. Schlisio. 2005. Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: developmental culling and cancer. Cancer Cell 8:155-167.
51. Lieubeau-Teillet, B., J. Rak, S. Jothy, O. Iliopoulos, W. Kaelin, and R. S. Kerbel. 1998. von Hippel-Lindau gene-mediated growth suppression and induction of differentiation in renal cell carcinoma cells grown as multicellular tumor spheroids. Cancer Res. 58:4957-4962.
52. Lonergan, K. M., O. Iliopoulos, M. Ohh, T. Kamura, R. C. Conaway, J. W. Conaway, and W. G. Kaelin, Jr. 1998. Regulation of hypoxia-inducible mRNAs by the von Hippel-Lindau tumor suppressor protein requires binding to complexes containing elongins B/C and Cul2. Mol. Cell. Biol. 18:732-741.
53. Ma, W., L. Tessarollo, S. B. Hong, M. Baba, E. Southon, T. C. Back, S. Spence, C. G. Lobe, N. Sharma, G. W. Maher, S. Pack, A. O. Vortmeyer, C. Guo, B. Zbar, and L. S. Schmidt. 2003. Hepatic vascular tumors, angiectasis in multiple organs, and impaired spermatogenesis in mice with conditional inactivation of the VHL gene. Cancer Res. 63:5320-5328.
54. Mandriota, S. J., K. J. Turner, D. R. Davies, P. G. Murray, N. V. Morgan, H. M. Sowter, C. C. Wykoff, E. R. Maher, A. L. Harris, P. J. Ratcliffe, and P. H. Maxwell. 2002. HIF activation identifies early lesions in VHL kidneys: evidence for site-specific tumor suppressor function in the nephron. Cancer Cell 1:459-468.
55. Maranchie, J. K., J. R. Vasselli, J. Riss, J. S. Bonifacino, W. M. Linehan, and R. D. Klausner. 2002. The contribution of VHL substrate binding and HIF1-α to the phenotype of VHL loss in renal cell carcinoma. Cancer Cell 1:247-255.
56. Masson, N., C. Willam, P. H. Maxwell, C. W. Pugh, and P. J. Ratcliffe. 2001. Independent function of two destruction domains in hypoxia-inducible factor-alpha chains activated by prolyl hydroxylation. EMBO J. 20:5197-5206.
57. Maxwell, P. H., M. S. Wiesener, G. W. Chang, S. C. Clifford, E. C. Vaux, M. E. Cockman, C. C. Wykoff, C. W. Pugh, E. R. Maher, and P. J. Ratcliffe. 1999. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399:271-275.
58. Min, J. H., H. Yang, M. Ivan, F. Gertler, W. G. Kaelin, Jr., and N. P. Pavletich. 2002. Structure of an HIF-1α-pVHL complex: hydroxyproline recognition in signaling. Science 296:1886-1889.
59. Naito, S., S. M. Walker, and I. J. Fidler. 1989. In vivo selection of human renal cell carcinoma cells with high metastatic potential in nude mice. Clin. Exp. Metastasis 7:381-389.
60. Nakamura, E., P. Abreu-e-Lima, Y. Awakura, T. Inoue, T. Kamoto, O. Ogawa, H. Kotani, T. Manabe, G. J. Zhang, K. Kondo, V. Nose, and W. G. Kaelin, Jr. 2006. Clusterin is a secreted marker for a hypoxia-inducible factor-independent function of the von Hippel-Lindau tumor suppressor protein. Am. J. Pathol 168:574-584.
61. Ohh, M., C. W. Park, M. Ivan, M. A. Hoffman, T. Y. Kim, L. E. Huang, N. Pavletich, V. Chau, and W. G. Kaelin. 2000. Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nat. Cell Biol. 2:423-427.
62. Ohh, M., Y. Takagi, T. Aso, C. E. Stebbins, N. P. Pavletich, B. Zbar, R. C. Conaway, J. W. Conaway, and W. G. Kaelin, Jr. 1999. Synthetic peptides define critical contacts between elongin C, elongin B, and the von Hippel-Lindau protein. J. Clin. Investig. 104:1583-1591.
63. Pause, A., S. Lee, K. M. Lonergan, and R. D. Klausner. 1998. The von Hippel-Lindau tumor suppressor gene is required for cell cycle exit upon serum withdrawal. Proc. Natl. Acad. Sci. USA 95:993-998.
64. Pause, A., S. Lee, R. A. Worrell, D. Y. Chen, W. H. Burgess, W. M. Linehan, and R. D. Klausner. 1997. 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 94:2156-2161.
65. Pescador, N., Y. Cuevas, S. Naranjo, M. Alcaide, D. Villar, M. O. Landazuri, and L. Del Peso. 2005. Identification of a functional hypoxia-responsive element that regulates the expression of the egl nine homologue 3 (egln3/phd3) gene. Biochem. J. 390:189-197.
66. Pollard, P. J., J. J. Briere, N. A. Alam, J. Barwell, E. Barclay, N. C. Wortham, T. Hunt, M. Mitchell, S. Olpin, S. J. Moat, I. P. Hargreaves, S. J. Heales, Y. L. Chung, J. R. Griffiths, A. Dalgleish, J. A. McGrath, M. J. Gleeson, S. V. Hodgson, R. Poulsom, P. Rustin, and I. P. Tomlinson. 2005. Accumulation of Krebs cycle intermediates and over-expression of HIF1α in tumours which result from germline FH and SDH mutations. Hum. Mol. Genet. 14:2231-2239.
67. Rankin, E. B., D. F. Higgins, J. A. Walisser, R. S. Johnson, C. A. Bradfield, and V. H. Haase. 2005. Inactivation of the arylhydrocarbon receptor nuclear translocator (Arnt) suppresses von Hippel-Lindau disease-associated vascular tumors in mice. Mol. Cell. Biol. 25:3163-3172.
68. Rathmell, W. K., M. M. Hickey, N. A. Bezman, C. A. Chmielecki, N. C. Carraway, and M. C. Simon. 2004. In vitro and in vivo models analyzing von Hippel-Lindau disease-specific mutations. Cancer Res. 64:8595-8603.
69. Raval, R. R., K. W. Lau, M. G. Tran, H. M. Sowter, S. J. Mandriota, J. L. Li, C. W. Pugh, P. H. Maxwell, A. L. Harris, and P. J. Ratcliffe. 2005. Contrast-ing properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma. Mol. Cell. Biol. 25:5675-5686.
70. Richard, S., R. Lidereau, and S. Giraud. 2004. The growing family of hereditary renal cell carcinoma. Nephrol. Dial. Transplant. 19:2954-2958.
71. Schoenfeld, A. R., E. J. Davidowitz, and R. D. Burk. 2000. Elongin BC complex prevents degradation of von Hippel-Lindau tumor suppressor gene products. Proc. Natl. Acad. Sci. USA 97:8507-8512.
72. Schofield, C. J., and P. J. Ratcliffe. 2004. Oxygen sensing by HIF hydroxylases. Nat. Rev. Mol. Cell. Biol. 5:343-354.
73. Selak, M. A., S. M. Armour, E. D. MacKenzie, H. Boulahbel, D. G. Watson, K. D. Mansfield, Y. Pan, M. C. Simon, C. B. Thompson, and E. Gottlieb. 2005. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase. Cancer Cell 7:77-85.
74. -/- renal cancer. Cancer Res. 65:5221-5230.
75. Staller, P., J. Sulitkova, J. Lisztwan, H. Moch, E. J. Oakeley, and W. Krek. 2003. Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL. Nature 425:307-311.
76. Stebbins, C. E., W. G. Kaelin, Jr., and N. P. Pavletich. 1999. Structure of the VHL-elongin C-elongin B complex: implications for VHL tumor suppressor function. Science 284:455-461.
77. Yu, F., S. B. White, Q. Zhao, and F. S. Lee. 2001. HIF-1α binding to VHL is regulated by stimulus-sensitive proline hydroxylation. Proc. Natl. Acad. Sci. USA 98:9630-9635.
78. Zagzag, D., B. Krishnamachary, H. Yee, H. Okuyama, L. Chiriboga, M. A. Ali, J. Melamed, and G. L. Semenza. 2005. Stromal cell-derived factor-1α 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. 65:6178-6188.
79. -/- tumors. Mol. Cancer Res. 2:89-95.