{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:14:16Z","timestamp":1780467256736,"version":"3.54.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2002,12,23]],"date-time":"2002-12-23T00:00:00Z","timestamp":1040601600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Cell Biol"],"published-print":{"date-parts":[[2003,1]]},"DOI":"10.1038\/ncb899","type":"journal-article","created":{"date-parts":[[2003,1,3]],"date-time":"2003-01-03T11:06:20Z","timestamp":1041591980000},"page":"64-70","source":"Crossref","is-referenced-by-count":287,"title":["Regulation of microtubule stability by the von Hippel-Lindau tumour suppressor protein pVHL"],"prefix":"10.1038","volume":"5","author":[{"given":"Alexander","family":"Hergovich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Lisztwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Barry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Ballschmieter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelm","family":"Krek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2002,12,23]]},"reference":[{"key":"BFncb899_CR1","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/nrc885","volume":"2","author":"WG Kaelin","year":"2002","unstructured":"Kaelin, W. G. Molecular basis of the VHL hereditary cancer syndrome. Nature Rev. Cancer 2, 673\u2013682 (2002).","journal-title":"Nature Rev. Cancer"},{"key":"BFncb899_CR2","doi-asserted-by":"publisher","first-page":"11661","DOI":"10.1073\/pnas.95.20.11661","volume":"95","author":"O Iliopoulos","year":"1998","unstructured":"Iliopoulos, O., Ohh, M. & Kaelin, W. G., Jr. pVHL19 is a biologically active product of the von Hippel-Lindau gene arising from internal translation initiation. Proc. Natl Acad. Sci. USA 95, 11661\u201311666 (1998).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncb899_CR3","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1038\/sj.onc.1202473","volume":"18","author":"C Blankenship","year":"1999","unstructured":"Blankenship, C., Naglich, J. G., Whaley, J. M., Seizinger, B. & Kley, N. Alternate choice of initiation codon produces a biologically active product of the von Hippel Lindau gene with tumor suppressor activity. Oncogene 18, 1529\u20131535 (1999).","journal-title":"Oncogene"},{"key":"BFncb899_CR4","doi-asserted-by":"publisher","first-page":"8817","DOI":"10.1073\/pnas.95.15.8817","volume":"95","author":"A Schoenfeld","year":"1998","unstructured":"Schoenfeld, A., Davidowitz, E. J. & Burk, R. D. 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\u20138822 (1998).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncb899_CR5","first-page":"743","volume":"55","author":"J Gao","year":"1995","unstructured":"Gao, J. et al. Cloning and characterization of a mouse gene with homology to the human von Hippel-Lindau disease tumor suppressor gene: implications for the potential organization of the human von Hippel-Lindau disease gene. Cancer Res. 55, 743\u2013747 (1995).","journal-title":"Cancer Res."},{"key":"BFncb899_CR6","doi-asserted-by":"publisher","first-page":"10595","DOI":"10.1073\/pnas.93.20.10595","volume":"93","author":"O Iliopoulos","year":"1996","unstructured":"Iliopoulos, O., Levy, A. P., Jiang, C., Kaelin, W. G. Jr., & Goldberg, M. A. Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein. Proc. Natl Acad. Sci. USA 93, 10595\u201310599 (1996).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncb899_CR7","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/20459","volume":"399","author":"PH Maxwell","year":"1999","unstructured":"Maxwell, P. H. et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399, 271\u2013275 (1999).","journal-title":"Nature"},{"key":"BFncb899_CR8","doi-asserted-by":"publisher","first-page":"10430","DOI":"10.1073\/pnas.190332597","volume":"97","author":"T Kamura","year":"2000","unstructured":"Kamura, T. et al. Activation of HIF1\u03b1 ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex. Proc. Natl Acad. Sci. USA 97, 10430\u201310435 (2000).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncb899_CR9","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/35017054","volume":"2","author":"M Ohh","year":"2000","unstructured":"Ohh, M. et al. Ubiquitination of hypoxia-inducible factor requires direct binding to the \u03b2-domain of the von Hippel-Lindau protein. Nature Cell Biol. 2, 423\u2013427 (2000).","journal-title":"Nature Cell Biol."},{"key":"BFncb899_CR10","doi-asserted-by":"publisher","first-page":"25733","DOI":"10.1074\/jbc.M002740200","volume":"275","author":"ME Cockman","year":"2000","unstructured":"Cockman, M. E. et al. Hypoxia inducible factor-\u03b1 binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein. J. Biol. Chem. 275, 25733\u201325741 (2000).","journal-title":"J. Biol. Chem."},{"key":"BFncb899_CR11","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1093\/hmg\/10.10.1029","volume":"10","author":"SC Clifford","year":"2001","unstructured":"Clifford, S. C. et al. Contrasting effects on HIF-1\u03b1 regulation by disease-causing pVHL mutations correlate with patterns of tumourigenesis in von Hippel-Lindau disease. Hum. Mol. Genet. 10, 1029\u20131038 (2001).","journal-title":"Hum. Mol. Genet."},{"key":"BFncb899_CR12","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1093\/hmg\/10.10.1019","volume":"10","author":"MA Hoffman","year":"2001","unstructured":"Hoffman, M. A. et al. von Hippel-Lindau protein mutants linked to type 2C VHL disease preserve the ability to downregulate HIF. Hum. Mol. Genet. 10, 1019\u20131027 (2001).","journal-title":"Hum. Mol. Genet."},{"key":"BFncb899_CR13","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1073\/pnas.93.5.1770","volume":"93","author":"S Lee","year":"1996","unstructured":"Lee, S. et al. Nuclear\/cytoplasmic localization of the von Hippel-Lindau tumor suppressor gene product is determined by cell density. Proc. Natl Acad. Sci. USA 93, 1770\u20131775 (1996).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncb899_CR14","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1128\/MCB.19.2.1486","volume":"19","author":"S Lee","year":"1999","unstructured":"Lee, S. et al. Transcription-dependent nuclear-cytoplasmic trafficking is required for the function of the von Hippel-Lindau tumor suppressor protein. Mol. Cell Biol. 19, 1486\u20131497 (1999).","journal-title":"Mol. Cell Biol."},{"key":"BFncb899_CR15","doi-asserted-by":"publisher","first-page":"2156","DOI":"10.1073\/pnas.94.6.2156","volume":"94","author":"A Pause","year":"1997","unstructured":"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 94, 2156\u20132161 (1997).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncb899_CR16","doi-asserted-by":"publisher","first-page":"6459","DOI":"10.1073\/pnas.92.14.6459","volume":"92","author":"DR Duan","year":"1995","unstructured":"Duan, D. R. et al. 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\u20136463 (1995).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncb899_CR17","doi-asserted-by":"publisher","first-page":"8991","DOI":"10.1074\/jbc.275.12.8991","volume":"275","author":"I Groulx","year":"2000","unstructured":"Groulx, I., Bonicalzi, M. E. & Lee, S. 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\u20139000 (2000).","journal-title":"J. Biol. Chem."},{"key":"BFncb899_CR18","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1038\/nm0895-822","volume":"1","author":"O Iliopoulos","year":"1995","unstructured":"Iliopoulos, O., Kibel, A., Gray, S. & Kaelin, W. G., Jr. Tumour suppression by the human von Hippel-Lindau gene product. Nature Med. 1, 822\u2013826 (1995).","journal-title":"Nature Med."},{"key":"BFncb899_CR19","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1016\/S1097-2765(00)80096-9","volume":"1","author":"M Ohh","year":"1998","unstructured":"Ohh, M. et al. The von Hippel-Lindau tumor suppressor protein is required for proper assembly of an extracellular fibronectin matrix. Mol. Cell 1, 959\u2013968 (1998).","journal-title":"Mol. Cell"},{"key":"BFncb899_CR20","first-page":"2816","volume":"60","author":"YH Shiao","year":"2000","unstructured":"Shiao, Y. H., Resau, J. H., Nagashima, K., Anderson, L. M. & Ramakrishna, G. The von Hippel-Lindau tumor suppressor targets to mitochondria. Cancer Res. 60, 2816\u20132819 (2000).","journal-title":"Cancer Res."},{"key":"BFncb899_CR21","first-page":"231","volume":"75","author":"M Los","year":"1996","unstructured":"Los, M. et al. Expression pattern of the von Hippel-Lindau protein in human tissues. Lab. Invest. 75, 231\u2013238 (1996).","journal-title":"Lab. Invest."},{"key":"BFncb899_CR22","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/S0046-8177(97)90035-6","volume":"28","author":"CL Corless","year":"1997","unstructured":"Corless, C. L., Kibel, A. S., Iliopoulos, O. & Kaelin, W. G., Jr. Immunostaining of the von Hippel-Lindau gene product in normal and neoplastic human tissues. Hum. Pathol. 28, 459\u2013464 (1997).","journal-title":"Hum. Pathol."},{"key":"BFncb899_CR23","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1002\/(SICI)1097-0215(19980925)78:1<62::AID-IJC11>3.0.CO;2-7","volume":"78","author":"Y Ye","year":"1998","unstructured":"Ye, Y. et al. Subcellular localization of the von Hippel-Lindau disease gene product is cell cycle-dependent. Int. J. Cancer 78, 62\u201369 (1998).","journal-title":"Int. J. Cancer"},{"key":"BFncb899_CR24","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1002\/1097-0215(20010215)91:4<457::AID-IJC1072>3.0.CO;2-P","volume":"91","author":"AR Schoenfeld","year":"2001","unstructured":"Schoenfeld, A. R., Davidowitz, E. J. & Burk, R. D. Endoplasmic reticulum\/cytosolic localization of von Hippel-Lindau gene products is mediated by a 64-amino acid region. Int. J. Cancer 91, 457\u2013467 (2001).","journal-title":"Int. J. Cancer"},{"key":"BFncb899_CR25","doi-asserted-by":"publisher","first-page":"1822","DOI":"10.1101\/gad.13.14.1822","volume":"13","author":"J Lisztwan","year":"1999","unstructured":"Lisztwan, J., Imbert, G., Wirbelauer, C., Gstaiger, M. & Krek, W. The von Hippel-Lindau tumor suppressor protein is a component of an E3 ubiquitin-protein ligase activity. Genes Dev. 13, 1822\u20131833 (1999).","journal-title":"Genes Dev."},{"key":"BFncb899_CR26","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/ng0594-85","volume":"7","author":"JR Gnarra","year":"1994","unstructured":"Gnarra, J. R. et al. Mutations of the VHL tumour suppressor gene in renal carcinoma. Nature Genet. 7, 85\u201390 (1994).","journal-title":"Nature Genet."},{"key":"BFncb899_CR27","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1002\/(SICI)1096-8628(19991119)87:2<163::AID-AJMG7>3.0.CO;2-A","volume":"87","author":"JF Bradley","year":"1999","unstructured":"Bradley, J. F., Collins, D. L., Schimke, R. N., Parrott, H. N. & Rothberg, P. G. Two distinct phenotypes caused by two different missense mutations in the same codon of the VHL gene. Am. J. Med. Genet. 87, 163\u2013167 (1999).","journal-title":"Am. J. Med. Genet."},{"key":"BFncb899_CR28","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1007\/BF00223868","volume":"95","author":"H Brauch","year":"1995","unstructured":"Brauch, H. et al. Von Hippel-Lindau (VHL) disease with pheochromocytoma in the Black Forest region of Germany: evidence for a founder effect. Hum. Genet. 95, 551\u2013556 (1995).","journal-title":"Hum. Genet."},{"key":"BFncb899_CR29","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1002\/humu.1380050109","volume":"5","author":"F Chen","year":"1995","unstructured":"Chen, F. et al. Germline mutations in the von Hippel-Lindau disease tumor suppressor gene: correlations with phenotype. Hum. Mutat. 5, 66\u201375 (1995).","journal-title":"Hum. Mutat."},{"key":"BFncb899_CR30","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1093\/hmg\/3.8.1303","volume":"3","author":"PA Crossey","year":"1994","unstructured":"Crossey, P. A. et al. Identification of intragenic mutations in the von Hippel-Lindau disease tumour suppressor gene and correlation with disease phenotype. Hum. Mol. Genet. 3, 1303\u20131308 (1994).","journal-title":"Hum. Mol. Genet."},{"key":"BFncb899_CR31","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1002\/(SICI)1098-1004(1996)8:4<348::AID-HUMU8>3.0.CO;2-3","volume":"8","author":"B Zbar","year":"1996","unstructured":"Zbar, B. et al. Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan. Hum. Mutat. 8, 348\u2013357 (1996).","journal-title":"Hum. Mutat."},{"key":"BFncb899_CR32","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1136\/jmg.32.12.934","volume":"32","author":"C Eng","year":"1995","unstructured":"Eng, C. et al. Mutations in the RET proto-oncogene and the von Hippel-Lindau disease tumour suppressor gene in sporadic and syndromic phaeochromocytomas. J. Med. Genet. 32, 934\u2013937 (1995).","journal-title":"J. Med. Genet."},{"key":"BFncb899_CR33","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1093\/nar\/26.1.256","volume":"26","author":"CJD Beroud","year":"1998","unstructured":"Beroud, C. J. D., Gallou, C., Staroz, F., Orfanelli, M.T. & Junien, C. Software and database for the analysis of mutations in the VHL gene. Nucleic Acids Research 26, 256\u2013258 (1998).","journal-title":"Nucleic Acids Research"},{"key":"BFncb899_CR34","first-page":"1942","volume":"60","author":"H Brauch","year":"2000","unstructured":"Brauch, H. et al. VHL alterations in human clear cell renal cell carcinoma: association with advanced tumor stage and a novel hot spot mutation. Cancer Res. 60, 1942\u20131948 (2000).","journal-title":"Cancer Res."},{"key":"BFncb899_CR35","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1097\/00043426-200202000-00018","volume":"24","author":"P Reichardt","year":"2002","unstructured":"Reichardt, P. et al. Recurrent polytopic chromaffin paragangliomas in a 9-year-old boy resulting from a novel germline mutation in the von Hippel-Lindau gene. J. Pediatr. Hematol. Oncol. 24, 145\u2013148 (2002).","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"BFncb899_CR36","doi-asserted-by":"publisher","first-page":"5319","DOI":"10.1128\/MCB.22.15.5319-5336.2002","volume":"22","author":"I Groulx","year":"2002","unstructured":"Groulx, I. & Lee, S. 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\u20135336 (2002).","journal-title":"Mol. Cell. Biol."},{"key":"BFncb899_CR37","doi-asserted-by":"publisher","first-page":"3331","DOI":"10.1002\/j.1460-2075.1991.tb04897.x","volume":"10","author":"W Krek","year":"1991","unstructured":"Krek, W. & Nigg, E. A. Mutations of p34cdc2 phosphorylation sites induce premature mitotic events in HeLa cells: evidence for a double block to p34cdc2 kinase activation in vertebrates. EMBO J. 10, 3331\u20133341 (1991).","journal-title":"EMBO J."},{"key":"BFncb899_CR38","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1093\/emboj\/17.2.368","volume":"17","author":"J Lisztwan","year":"1998","unstructured":"Lisztwan, J. et al. Association of human CUL-1 and ubiquitin-conjugating enzyme CDC34 with the F-box protein p45(SKP2): evidence for evolutionary conservation in the subunit composition of the CDC34-SCF pathway. EMBO J. 17, 368\u2013383 (1998).","journal-title":"EMBO J."}],"container-title":["Nature Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/ncb899.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ncb899","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ncb899.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T19:52:53Z","timestamp":1684439573000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncb899"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,12,23]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,1]]}},"alternative-id":["BFncb899"],"URL":"https:\/\/doi.org\/10.1038\/ncb899","relation":{},"ISSN":["1465-7392","1476-4679"],"issn-type":[{"value":"1465-7392","type":"print"},{"value":"1476-4679","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,12,23]]}}}