This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lonergan, K. M.
Right arrow Articles by Kaelin, W. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lonergan, K. M.
Right arrow Articles by Kaelin, W. G., Jr.

 Previous Article  |  Next Article 

Mol Cell Biol, February 1998, p. 732-741, Vol. 18, No. 2
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Regulation of Hypoxia-Inducible mRNAs by the von Hippel-Lindau Tumor Suppressor Protein Requires Binding to Complexes Containing Elongins B/C and Cul2

Kim M. Lonergan,1,2 Othon Iliopoulos,1,2 Michael Ohh,1,2 Takumi Kamura,3 Ronald C. Conaway,3 Joan Weliky Conaway,3,4,5 and William G. Kaelin Jr.1,2,*

Dana-Farber Cancer Institute1 and Brigham and Women's Hospital, Harvard Medical School,2 Boston, Massachusetts 02115; Program in Molecular and Cell Biology3 and Howard Hughes Medical Institute,4 Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104; and Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 731905

Received 15 September 1997/Accepted 9 November 1997

The von Hippel-Lindau tumor suppressor protein (pVHL) binds to elongins B and C and posttranscriptionally regulates the accumulation of hypoxia-inducible mRNAs under normoxic (21% O2) conditions. Here we report that pVHL binds, via elongin C, to the human homolog of the Caenorhabditis elegans Cul2 protein. Coimmunoprecipitation and chromatographic copurification data suggest that pVHL-Cul2 complexes exist in native cells. pVHL mutants that were unable to bind to complexes containing elongin C and Cul2 were likewise unable to inhibit the accumulation of hypoxia-inducible mRNAs. A model for the regulation of hypoxia-inducible mRNAs by pVHL is presented based on the apparent similarity of elongin C and Cul2 to Skp1 and Cdc53, respectively. These latter proteins form complexes that target specific proteins for ubiquitin-dependent proteolysis.

* Corresponding author. Mailing address: Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, 44 Binney St., Mayer 657, Boston, MA 02115. Phone: (617) 632-3975. Fax: (617) 632-4381. E-mail: william_kaelin{at}dfci.harvard.edu.




This article has been cited by other articles:

  • Gergics, P., Patocs, A., Toth, M., Igaz, P., Szucs, N., Liko, I., Fazakas, F., Szabo, I., Kovacs, B., Glaz, E., Racz, K. (2009). Germline VHL gene mutations in Hungarian families with von Hippel-Lindau disease and patients with apparently sporadic unilateral pheochromocytomas. Eur J Endocrinol 161: 495-502 [Abstract] [Full Text]  
  • Xiao, W., Ai, J., Habermacher, G., Volpert, O., Yang, X., Zhang, A.-y., Hahn, J., Cai, X., Wang, Z. (2009). U19/Eaf2 Binds to and Stabilizes von Hippel-Lindau Protein. Cancer Res. 69: 2599-2606 [Abstract] [Full Text]  
  • Piessevaux, J., De Ceuninck, L., Catteeuw, D., Peelman, F., Tavernier, J. (2008). Elongin B/C Recruitment Regulates Substrate Binding by CIS. J. Biol. Chem. 283: 21334-21346 [Abstract] [Full Text]  
  • Maeda, Y., Suzuki, T., Pan, X., Chen, G., Pan, S., Bartman, T., Whitsett, J. A. (2008). CUL2 Is Required for the Activity of Hypoxia-inducible Factor and Vasculogenesis. J. Biol. Chem. 283: 16084-16092 [Abstract] [Full Text]  
  • Mahrour, N., Redwine, W. B., Florens, L., Swanson, S. K., Martin-Brown, S., Bradford, W. D., Staehling-Hampton, K., Washburn, M. P., Conaway, R. C., Conaway, J. W. (2008). Characterization of Cullin-box Sequences That Direct Recruitment of Cul2-Rbx1 and Cul5-Rbx2 Modules to Elongin BC-based Ubiquitin Ligases. J. Biol. Chem. 283: 8005-8013 [Abstract] [Full Text]  
  • Khacho, M., Mekhail, K., Pilon-Larose, K., Payette, J., Lee, S. (2008). Cancer-Causing Mutations in a Novel Transcription-Dependent Nuclear Export Motif of VHL Abrogate Oxygen-Dependent Degradation of Hypoxia-Inducible Factor. Mol. Cell. Biol. 28: 302-314 [Abstract] [Full Text]  
  • Turcotte, S., Giaccia, A. J. (2008). Targeted Therapy for the Loss of the Tumor Suppressor Gene von Hippel-Lindau through Synthetic Lethality. Am Soc Clin Oncol Ed Book 2008: e15-e18 [Abstract] [Full Text]  
  • Wu, K. L., Miao, H., Khan, S. (2007). JAK kinases promote invasiveness in VHL-mediated renal cell carcinoma by a suppressor of cytokine signaling-regulated, HIF-independent mechanism. Am. J. Physiol. Renal Physiol. 293: F1836-F1846 [Abstract] [Full Text]  
  • Li, L., Zhang, L., Zhang, X., Yan, Q., Minamishima, Y. A., Olumi, A. F., Mao, M., Bartz, S., Kaelin, W. G. Jr. (2007). Hypoxia-Inducible Factor Linked to Differential Kidney Cancer Risk Seen with Type 2A and Type 2B VHL Mutations. Mol. Cell. Biol. 27: 5381-5392 [Abstract] [Full Text]  
  • Luo, K., Ehrlich, E., Xiao, Z., Zhang, W., Ketner, G., Yu, X.-F. (2007). Adenovirus E4orf6 assembles with Cullin5-ElonginB-ElonginC E3 ubiquitin ligase through an HIV/SIV Vif-like BC-box to regulate p53. FASEB J. 21: 1742-1750 [Abstract] [Full Text]  
  • Fu, J., Menzies, K., Freeman, R. S., Taubman, M. B. (2007). EGLN3 Prolyl Hydroxylase Regulates Skeletal Muscle Differentiation and Myogenin Protein Stability. J. Biol. Chem. 282: 12410-12418 [Abstract] [Full Text]  
  • Evans, A. J., Russell, R. C., Roche, O., Burry, T. N., Fish, J. E., Chow, V. W. K., Kim, W. Y., Saravanan, A., Maynard, M. A., Gervais, M. L., Sufan, R. I., Roberts, A. M., Wilson, L. A., Betten, M., Vandewalle, C., Berx, G., Marsden, P. A., Irwin, M. S., Teh, B. T., Jewett, M. A. S., Ohh, M. (2007). VHL Promotes E2 Box-Dependent E-Cadherin Transcription by HIF-Mediated Regulation of SIP1 and Snail. Mol. Cell. Biol. 27: 157-169 [Abstract] [Full Text]  
  • Iliopoulos, O. (2006). Molecular Biology of Renal Cell Cancer and the Identification of Therapeutic Targets. JCO 24: 5593-5600 [Abstract] [Full Text]  
  • Pollard, P. J., El-Bahrawy, M., Poulsom, R., Elia, G., Killick, P., Kelly, G., Hunt, T., Jeffery, R., Seedhar, P., Barwell, J., Latif, F., Gleeson, M. J., Hodgson, S. V., Stamp, G. W., Tomlinson, I. P. M., Maher, E. R. (2006). Expression of HIF-1{alpha}, HIF-2{alpha} (EPAS1), and Their Target Genes in Paraganglioma and Pheochromocytoma with VHL and SDH Mutations. J. Clin. Endocrinol. Metab. 91: 4593-4598 [Abstract] [Full Text]  
  • Mosher, R. A., Durrant, W. E., Wang, D., Song, J., Dong, X. (2006). A Comprehensive Structure-Function Analysis of Arabidopsis SNI1 Defines Essential Regions and Transcriptional Repressor Activity. Plant Cell 18: 1750-1765 [Abstract] [Full Text]  
  • Woodward, E. R, Maher, E. R (2006). Von Hippel-Lindau disease and endocrine tumour susceptibility.. Endocr Relat Cancer 13: 415-425 [Abstract] [Full Text]  
  • Ribar, B., Prakash, L., Prakash, S. (2006). Requirement of ELC1 for RNA Polymerase II Polyubiquitylation and Degradation in Response to DNA Damage in Saccharomyces cerevisiae.. Mol. Cell. Biol. 26: 3999-4005 [Abstract] [Full Text]  
  • Maher, E. R. (2006). Genetics of phaeochromocytoma. Br Med Bull 79-80: 141-151 [Abstract] [Full Text]  
  • Nakaigawa, N., Yao, M., Baba, M., Kato, S., Kishida, T., Hattori, K., Nagashima, Y., Kubota, Y. (2006). Inactivation of von Hippel-Lindau Gene Induces Constitutive Phosphorylation of MET Protein in Clear Cell Renal Carcinoma.. Cancer Res. 66: 3699-3705 [Abstract] [Full Text]  
  • Hopfer, U., Hopfer, H., Jablonski, K., Stahl, R. A. K., Wolf, G. (2006). The Novel WD-repeat Protein Morg1 Acts as a Molecular Scaffold for Hypoxia-inducible Factor Prolyl Hydroxylase 3 (PHD3). J. Biol. Chem. 281: 8645-8655 [Abstract] [Full Text]  
  • Nakamura, E., Abreu-e-Lima, P., Awakura, Y., Inoue, T., Kamoto, T., Ogawa, O., Kotani, H., Manabe, T., Zhang, G.-J., Kondo, K., Nose, V., Kaelin, W. G. 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 [Abstract] [Full Text]  
  • Bindra, R. S., Gibson, S. L., Meng, A., Westermark, U., Jasin, M., Pierce, A. J., Bristow, R. G., Classon, M. K., Glazer, P. M. (2005). Hypoxia-Induced Down-regulation of BRCA1 Expression by E2Fs. Cancer Res. 65: 11597-11604 [Abstract] [Full Text]  
  • Cohen, H. T., McGovern, F. J. (2005). Renal-Cell Carcinoma. NEJM 353: 2477-2490 [Full Text]  
  • Lolkema, M. P., Gervais, M. L., Snijckers, C. M., Hill, R. P., Giles, R. H., Voest, E. E., Ohh, M. (2005). Tumor Suppression by the von Hippel-Lindau Protein Requires Phosphorylation of the Acidic Domain. J. Biol. Chem. 280: 22205-22211 [Abstract] [Full Text]  
  • KAELIN, W.G. JR. (2005). The von Hippel-Lindau Tumor Suppressor Protein: Roles in Cancer and Oxygen Sensing. Cold Spring Harb Symp Quant Biol 70: 159-166 [Abstract]  
  • Kim, W. Y., Kaelin, W. G. (2004). Role of VHL Gene Mutation in Human Cancer. JCO 22: 4991-5004 [Abstract] [Full Text]  
  • Bindra, R. S., Schaffer, P. J., Meng, A., Woo, J., Maseide, K., Roth, M. E., Lizardi, P., Hedley, D. W., Bristow, R. G., Glazer, P. M. (2004). Down-Regulation of Rad51 and Decreased Homologous Recombination in Hypoxic Cancer Cells. Mol. Cell. Biol. 24: 8504-8518 [Abstract] [Full Text]  
  • Ferrara, N. (2004). Vascular Endothelial Growth Factor: Basic Science and Clinical Progress. Endocr. Rev. 25: 581-611 [Abstract] [Full Text]  
  • Sufan, R. I., Jewett, M. A. S., Ohh, M. (2004). The role of von Hippel-Lindau tumor suppressor protein and hypoxia in renal clear cell carcinoma. Am. J. Physiol. Renal Physiol. 287: F1-F6 [Abstract] [Full Text]  
  • Stickle, N. H., Chung, J., Klco, J. M., Hill, R. P., Kaelin, W. G. Jr., Ohh, M. (2004). pVHL Modification by NEDD8 Is Required for Fibronectin Matrix Assembly and Suppression of Tumor Development. Mol. Cell. Biol. 24: 3251-3261 [Abstract] [Full Text]  
  • Turcotte, S., Desrosiers, R. R., Beliveau, R. (2004). Hypoxia upregulates von Hippel-Lindau tumor-suppressor protein through RhoA-dependent activity in renal cell carcinoma. Am. J. Physiol. Renal Physiol. 286: F338-F348 [Abstract] [Full Text]  
  • Massfelder, T., Lang, H., Schordan, E., Lindner, V., Rothhut, S., Welsch, S., Simon-Assmann, P., Barthelmebs, M., Jacqmin, D., Helwig, J.-J. (2004). Parathyroid Hormone-Related Protein Is an Essential Growth Factor for Human Clear Cell Renal Carcinoma and a Target for the von Hippel-Lindau Tumor Suppressor Gene. Cancer Res. 64: 180-188 [Abstract] [Full Text]  
  • Van Dort, C., Zhao, P., Parmelee, K., Capps, B., Poel, A., Listenberger, L., Kossoris, J., Wasilevich, B., Murrey, D., Clare, P., Burnatowska-Hledin, M. (2003). VACM-1, a cul-5 gene, inhibits cellular growth by a mechanism that involves MAPK and p53 signaling pathways. Am. J. Physiol. Cell Physiol. 285: C1386-C1396 [Abstract] [Full Text]  
  • Kaelin, W. G. Jr. (2003). The von Hippel-Lindau Gene, Kidney Cancer, and Oxygen Sensing. J. Am. Soc. Nephrol. 14: 2703-2711 [Abstract] [Full Text]  
  • Ma, W., Tessarollo, L., Hong, S.-B., Baba, M., Southon, E., Back, T. C., Spence, S., Lobe, C. G., Sharma, N., Maher, G. W., Pack, S., Vortmeyer, A. O., Guo, C., Zbar, B., Schmidt, L. S. (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 [Abstract] [Full Text]  
  • Michel, J. J., McCarville, J. F., Xiong, Y. (2003). A Role for Saccharomyces cerevisiae Cul8 Ubiquitin Ligase in Proper Anaphase Progression. J. Biol. Chem. 278: 22828-22837 [Abstract] [Full Text]  
  • Maynard, M. A., Qi, H., Chung, J., Lee, E. H. L., Kondo, Y., Hara, S., Conaway, R. C., Conaway, J. W., Ohh, M. (2003). Multiple Splice Variants of the Human HIF-3alpha Locus Are Targets of the von Hippel-Lindau E3 Ubiquitin Ligase Complex. J. Biol. Chem. 278: 11032-11040 [Abstract] [Full Text]  
  • Rui, L., Yuan, M., Frantz, D., Shoelson, S., White, M. F. (2002). SOCS-1 and SOCS-3 Block Insulin Signaling by Ubiquitin-mediated Degradation of IRS1 and IRS2. J. Biol. Chem. 277: 42394-42398 [Abstract] [Full Text]  
  • Bodmer, D., van den Hurk, W., van Groningen, J. J. M., Eleveld, M. J., Martens, G. J. M., Weterman, M. A. J., Geurts van Kessel, A. (2002). Understanding familial and non-familial renal cell cancer. Hum Mol Genet 11: 2489-2498 [Abstract] [Full Text]  
  • Dollfus, H., Massin, P., Taupin, P., Nemeth, C., Amara, S., Giraud, S., Beroud, C., Dureau, P., Gaudric, A., Landais, P., Richard, S. (2002). Retinal Hemangioblastoma in von Hippel-Lindau Disease: A Clinical and Molecular Study. IOVS 43: 3067-3074 [Abstract] [Full Text]  
  • Brower, C. S., Sato, S., Tomomori-Sato, C., Kamura, T., Pause, A., Stearman, R., Klausner, R. D., Malik, S., Lane, W. S., Sorokina, I., Roeder, R. G., Conaway, J. W., Conaway, R. C. (2002). Mammalian mediator subunit mMED8 is an Elongin BC-interacting protein that can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin ligase. Proc. Natl. Acad. Sci. USA 99: 10353-10358 [Abstract] [Full Text]  
  • Groulx, I., Lee, S. (2002). Oxygen-Dependent Ubiquitination and Degradation of Hypoxia-Inducible Factor Requires Nuclear-Cytoplasmic Trafficking of the von Hippel-Lindau Tumor Suppressor Protein. Mol. Cell. Biol. 22: 5319-5336 [Abstract] [Full Text]  
  • Li, B., Ruiz, J. C., Chun, K. T. (2002). CUL-4A Is Critical for Early Embryonic Development. Mol. Cell. Biol. 22: 4997-5005 [Abstract] [Full Text]  
  • Fedele, A. O., Whitelaw, M. L., Peet, D. J. (2002). Regulation of Gene Expression by the Hypoxia-Inducible Factors. Mol. Interv. 2: 229-243 [Abstract] [Full Text]  
  • Zatyka, M., da Silva, N. F., Clifford, S. C., Morris, M. R., Wiesener, M. S., Eckardt, K.-U., Houlston, R. S., Richards, F. M., Latif, F., Maher, E. R. (2002). Identification of Cyclin D1 and Other Novel Targets for the von Hippel-Lindau Tumor Suppressor Gene by Expression Array Analysis and Investigation of Cyclin D1 Genotype as a Modifier in von Hippel-Lindau Disease. Cancer Res. 62: 3803-3811 [Abstract] [Full Text]  
  • Zatyka, M, Morrissey, C, Kuzmin, I, Lerman, M I, Latif, F, Richards, F M, Maher, E R (2002). Genetic and functional analysis of the von Hippel-Lindau (VHL) tumour suppressor gene promoter. J. Med. Genet. 39: 463-472 [Abstract] [Full Text]  
  • Bindra, R. S., Vasselli, J. R., Stearman, R., Linehan, W. M., Klausner, R. D. (2002). VHL-mediated Hypoxia Regulation of Cyclin D1 in Renal Carcinoma Cells. Cancer Res. 62: 3014-3019 [Abstract] [Full Text]  
  • Hansen, W. J., Ohh, M., Moslehi, J., Kondo, K., Kaelin, W. G., Welch, W. J. (2002). Diverse Effects of Mutations in Exon II of the von Hippel-Lindau (VHL) Tumor Suppressor Gene on the Interaction of pVHL with the Cytosolic Chaperonin and pVHL-Dependent Ubiquitin Ligase Activity. Mol. Cell. Biol. 22: 1947-1960 [Abstract] [Full Text]  
  • Bauer, A. L., Paulding, W. R., Striet, J. B., Schnell, P. O., Czyzyk-Krzeska, M. F. (2002). Endogenous von Hippel-Lindau Tumor Suppressor Protein Regulates Catecholaminergic Phenotype in PC12 Cells. Cancer Res. 62: 1682-1687 [Abstract] [Full Text]  
  • Pioli, P. A., Rigby, W. F. C. (2001). The Von Hippel-Lindau Protein Interacts with Heteronuclear Ribonucleoprotein A2 and Regulates Its Expression. J. Biol. Chem. 276: 40346-40352 [Abstract] [Full Text]  
  • Yang, H., Kaelin, W. G. Jr. (2001). Molecular Pathogenesis of the Von Hippel-Lindau Hereditary Cancer Syndrome: Implications for Oxygen Sensing. Cell Growth Differ. 12: 447-455 [Full Text]  
  • Hoffman, M. A., Ohh, M., Yang, H., Klco, J. M., Ivan, M., Kaelin, W. G. 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 [Abstract] [Full Text]  
  • Clifford, S. C., Cockman, M. E., Smallwood, A. C., Mole, D. R., Woodward, E. R., Maxwell, P. H., Ratcliffe, P. J., Maher, E. R. (2001). Contrasting effects on HIF-1{{alpha}} regulation by disease-causing pVHL mutations correlate with patterns of tumourigenesis in von Hippel-Lindau disease. Hum Mol Genet 10: 1029-1038 [Abstract] [Full Text]  
  • Yu, F., White, S. B., Zhao, Q., Lee, F. S. (2001). Dynamic, Site-specific Interaction of Hypoxia-inducible Factor-1{{alpha}} with the von Hippel-Lindau Tumor Suppressor Protein. Cancer Res. 61: 4136-4142 [Abstract] [Full Text]  
  • KARUMANCHI, S. A., JIANG, L., KNEBELMANN, B., STUART-TILLEY, A. K., ALPER, S. L., SUKHATME, V. P. (2001). VHL tumor suppressor regulates Cl-/HCO3- exchange and Na+/H+ exchange activities in renal carcinoma cells. Physiol. Genomics 5: 119-128 [Abstract] [Full Text]  
  • Hockel, M., Vaupel, P. (2001). Tumor Hypoxia: Definitions and Current Clinical, Biologic, and Molecular Aspects. JNCI J Natl Cancer Inst 93: 266-276 [Abstract] [Full Text]  
  • Davidowitz, E. J., Schoenfeld, A. R., Burk, R. D. (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 [Abstract] [Full Text]  
  • Kamura, T., Sato, S., Iwai, K., Czyzyk-Krzeska, M., Conaway, R. C., Conaway, J. W. (2000). Activation of HIF1alpha ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex. Proc. Natl. Acad. Sci. USA 10.1073/pnas.190332597v1 [Abstract] [Full Text]  
  • Schoenfeld, A. R., Davidowitz, E. J., Burk, R. D. (2000). Elongin BC complex prevents degradation of von Hippel-Lindau tumor suppressor gene products. Proc. Natl. Acad. Sci. USA 97: 8507-8512 [Abstract] [Full Text]  
  • Martinez, A, Fullwood, P, Kondo, K, Kishida, T, Yao, M, Maher, E R, Latif, F (2000). Role of chromosome 3p12-p21 tumour suppressor genes in clear cell renal cell carcinoma: analysis of VHL dependent and VHL independent pathways of tumorigenesis. Mol. Pathol. 53: 137-144 [Abstract] [Full Text]  
  • Woodward, E. R, Clifford, S. C, Astuti, D., Affara, N. A, Maher, E. R (2000). Familial clear cell renal cell carcinoma (FCRC): clinical features and mutation analysis of the VHL, MET, and CUL2 candidate genes. J. Med. Genet. 37: 348-353 [Abstract] [Full Text]  
  • Koth, C. M., Botuyan, M. V., Moreland, R. J., Jansma, D. B., Conaway, J. W., Conaway, R. C., Chazin, W. J., Friesen, J. D., Arrowsmith, C. H., Edwards, A. M. (2000). Elongin from Saccharomyces cerevisiae. J. Biol. Chem. 275: 11174-11180 [Abstract] [Full Text]  
  • Groulx, I., Bonicalzi, M.-E., Lee, S. (2000). Ran-mediated Nuclear Export of the von Hippel-Lindau Tumor Suppressor Protein Occurs Independently of Its Assembly with Cullin-2. J. Biol. Chem. 275: 8991-9000 [Abstract] [Full Text]  
  • Lopez de Heredia, M., Izquierdo, J. M., Cuezva, J. M. (2000). A Conserved Mechanism for Controlling the Translation of beta -F1-ATPase mRNA between the Fetal Liver and Cancer Cells. J. Biol. Chem. 275: 7430-7437 [Abstract] [Full Text]  
  • Wu, K., Fuchs, S. Y., Chen, A., Tan, P., Gomez, C., Ronai, Z.'e., Pan, Z.-Q. (2000). The SCFHOS/beta -TRCP-ROC1 E3 Ubiquitin Ligase Utilizes Two Distinct Domains within CUL1 for Substrate Targeting and Ubiquitin Ligation. Mol. Cell. Biol. 20: 1382-1393 [Abstract] [Full Text]  
  • Wada, H., Yeh, E. T. H., Kamitani, T. (1999). The von Hippel-Lindau Tumor Suppressor Gene Product Promotes, but Is Not Essential for, NEDD8 Conjugation to Cullin-2. J. Biol. Chem. 274: 36025-36029 [Abstract] [Full Text]  
  • Wilkinson, K. D. (1999). Ubiquitin-Dependent Signaling: The Role of Ubiquitination in the Response of Cells to Their Environment.. J. Nutr. 129: 1933-1936 [Abstract] [Full Text]  
  • Iwai, K., Yamanaka, K., Kamura, T., Minato, N., Conaway, R. C., Conaway, J. W., Klausner, R. D., Pause, A. (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 [Abstract] [Full Text]  
  • Kroll, S. L., Paulding, W. R., Schnell, P. O., Barton, M. C., Conaway, J.W., Conaway, R. C., Czyzyk-Krzeska, M. F. (1999). von Hippel-Lindau Protein Induces Hypoxia-regulated Arrest of Tyrosine Hydroxylase Transcript Elongation in Pheochromocytoma Cells. J. Biol. Chem. 274: 30109-30114 [Abstract] [Full Text]  
  • Koochekpour, S., Jeffers, M., Wang, P. H., Gong, C., Taylor, G. A., Roessler, L. M., Stearman, R., Vasselli, J. R., Stetler-Stevenson, W. G., Kaelin, W. G. Jr., Linehan, W. M., Klausner, R. D., Gnarra, J. R., Vande Woude, G. F. (1999). The von Hippel-Lindau Tumor Suppressor Gene Inhibits Hepatocyte Growth Factor/Scatter Factor-Induced Invasion and Branching Morphogenesis in Renal Carcinoma Cells. Mol. Cell. Biol. 19: 5902-5912 [Abstract] [Full Text]  
  • Duerr, E.-M., Gimm, O., Neuberg, D. S., Kum, J. B., Clifford, S. C., Toledo, S. P. A., Maher, E. R., Dahia, P. L. M., Eng, C. (1999). Differences in Allelic Distribution of Two Polymorphisms in the VHL-Associated Gene CUL2 in Pheochromocytoma Patients without Somatic CUL2 Mutations. J. Clin. Endocrinol. Metab. 84: 3207-3211 [Abstract] [Full Text]  
  • Pause, A., Peterson, B., Schaffar, G., Stearman, R., Klausner, R. D. (1999). Studying interactions of four proteins in the yeast two-hybrid system: Structural resemblance of the pVHL/elongin BC/hCUL-2 complex with the ubiquitin ligase complex SKP1/cullin/F-box protein. Proc. Natl. Acad. Sci. USA 96: 9533-9538 [Abstract] [Full Text]  
  • Lisztwan, J., Imbert, G., Wirbelauer, C., Gstaiger, M., Krek, W. (1999). The von Hippel-Lindau tumor suppressor protein is a component of an E3 ubiquitin-protein ligase activity. Genes Dev. 13: 1822-1833 [Abstract] [Full Text]  
  • Liakopoulos, D., Busgen, T., Brychzy, A., Jentsch, S., Pause, A. (1999). Conjugation of the ubiquitin-like protein NEDD8 to cullin-2 is linked to von Hippel-Lindau tumor suppressor function. Proc. Natl. Acad. Sci. USA 96: 5510-5515 [Abstract] [Full Text]  
  • Brower, C. S., Shilatifard, A., Mather, T., Kamura, T., Takagi, Y., Haque, D., Treharne, A., Foundling, S. I., Conaway, J. W., Conaway, R. C. (1999). The Elongin B Ubiquitin Homology Domain. IDENTIFICATION OF ELONGIN B SEQUENCES IMPORTANT FOR INTERACTION WITH ELONGIN C. J. Biol. Chem. 274: 13629-13636 [Abstract] [Full Text]  
  • Ananth, S., Knebelmann, B., Gruning, W., Dhanabal, M., Walz, G., Stillman, I. E., Sukhatme, V. P. (1999). Transforming Growth Factor {beta}1 Is a Target for the von Hippel-Lindau Tumor Suppressor and a Critical Growth Factor for Clear Cell Renal Carcinoma. Cancer Res. 59: 2210-2216 [Abstract] [Full Text]  
  • Kamura, T., Koepp, D. M., Conrad, M. N., Skowyra, D., Moreland, R. J., Iliopoulos, O., Lane, W. S., Kaelin Jr., W. G., Elledge, S. J., Conaway, R. C., Harper, J. W., Conaway, J. W. (1999). Rbx1, a Component of the VHL Tumor Suppressor Complex and SCF Ubiquitin Ligase. Science 284: 657-661 [Abstract] [Full Text]  
  • Zhang, J.-G., Farley, A., Nicholson, S. E., Willson, T. A., Zugaro, L. M., Simpson, R. J., Moritz, R. L., Cary, D., Richardson, R., Hausmann, G., Kile, B. J., Kent, S. B. H., Alexander, W. S., Metcalf, D., Hilton, D. J., Nicola, N. A., Baca, M. (1999). The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation. Proc. Natl. Acad. Sci. USA 96: 2071-2076 [Abstract] [Full Text]  
  • Gorospe, M., Egan, J. M., Zbar, B., Lerman, M., Geil, L., Kuzmin, I., Holbrook, N. J. (1999). Protective Function of von Hippel-Lindau Protein against Impaired Protein Processing in Renal Carcinoma Cells. Mol. Cell. Biol. 19: 1289-1300 [Abstract] [Full Text]  
  • Lee, S., Neumann, M., Stearman, R., Stauber, R., Pause, A., Pavlakis, G. N., Klausner, R. D. (1999). Transcription-Dependent Nuclear-Cytoplasmic Trafficking Is Required for the Function of the von Hippel-Lindau Tumor Suppressor Protein. Mol. Cell. Biol. 19: 1486-1497 [Abstract] [Full Text]  
  • Kamura, T., Sato, S., Haque, D., Liu, L., Kaelin Jr., W. G., Conaway, R. C., Conaway, J. W. (1998). The Elongin BC complex interacts with the conserved SOCS-box motif present in members of the SOCS, ras, WD-40 repeat, and ankyrin repeat families. Genes Dev. 12: 3872-3881 [Abstract] [Full Text]  
  • Shilatifard, A. (1998). Factors regulating the transcriptional elongation activity of RNA polymerase II. FASEB J. 12: 1437-1446 [Abstract] [Full Text]  
  • Iliopoulos, O., Ohh, M., Kaelin, W. G. Jr. (1998). pVHL19 is a biologically active product of the von Hippel-Lindau gene arising from internal translation initiation. Proc. Natl. Acad. Sci. USA 95: 11661-11666 [Abstract] [Full Text]  
  • Du, M., Sansores-Garcia, L., Zu, Z., Wu, K. K.-y. (1998). Cloning and Expression Analysis of a Novel Salicylate Suppressible Gene, Hs-CUL-3, a Member of Cullin/Cdc53 Family. J. Biol. Chem. 273: 24289-24292 [Abstract] [Full Text]  
  • Schoenfeld, A., Davidowitz, E. J., Burk, R. D. (1998). A second major native von Hippel-Lindau gene product, initiated from an internal translation start site, functions as a tumor suppressor. Proc. Natl. Acad. Sci. USA 95: 8817-8822 [Abstract] [Full Text]  
  • Teng-umnuay, P., Morris, H. R., Dell, A., Panico, M., Paxton, T., West, C. M. (1998). The Cytoplasmic F-box Binding Protein SKP1 Contains a Novel Pentasaccharide Linked to Hydroxyproline in Dictyostelium. J. Biol. Chem. 273: 18242-18249 [Abstract] [Full Text]  
  • Lyapina, S. A., Correll, C. C., Kipreos, E. T., Deshaies, R. J. (1998). Human CUL1 forms an evolutionarily conserved ubiquitin ligase complex (SCF) with SKP1 and an F-box protein. Proc. Natl. Acad. Sci. USA 95: 7451-7456 [Abstract] [Full Text]  
  • Cockman, M. E., Masson, N., Mole, D. R., Jaakkola, P., Chang, G.-W., Clifford, S. C., Maher, E. R., Pugh, C. W., Ratcliffe, P. J., Maxwell, P. H. (2000). Hypoxia Inducible Factor-alpha Binding and Ubiquitylation by the von Hippel-Lindau Tumor Suppressor Protein. J. Biol. Chem. 275: 25733-25741 [Abstract] [Full Text]  
  • Bonicalzi, M.-E., Groulx, I., de Paulsen, N., Lee, S. (2001). Role of Exon 2-encoded beta -Domain of the von Hippel-Lindau Tumor Suppressor Protein. J. Biol. Chem. 276: 1407-1416 [Abstract] [Full Text]  
  • Chen, A., Wu, K., Fuchs, S. Y., Tan, P., Gomez, C., Pan, Z.-Q. (2000). The Conserved RING-H2 Finger of ROC1 Is Required for Ubiquitin Ligation. J. Biol. Chem. 275: 15432-15439 [Abstract] [Full Text]  
  • Kamura, T., Sato, S., Iwai, K., Czyzyk-Krzeska, M., Conaway, R. C., Conaway, J. W. (2000). Activation of HIF1alpha ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex. Proc. Natl. Acad. Sci. USA 97: 10430-10435 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»