The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Nikola P Pavletich - One of the best experts on this subject based on the ideXlab platform.
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ubiquitination of hypoxia inducible factor requires direct binding to the β domain of the von hippel lindau protein
Nature Cell Biology, 2000Co-Authors: Michael Ohh, Nikola P Pavletich, Cheol Won Park, Mircea Ivan, Michael A Hoffman, Taeyou Kim, Eric L HuangAbstract:von Hippel-Lindau (VHL) disease is a hereditary Cancer Syndrome that is characterized by the development of multiple vascular tumors and is caused by inactivation of the von Hippel-Lindau protein (pVHL). Here we show that pVHL, through its beta-domain, binds directly to hypoxia-inducible factor (HIF), thereby targeting HIF for ubiquitination in an alpha-domain-dependent manner. This is the first function to be ascribed to the pVHL beta-domain. Furthermore, we provide the first direct evidence that pVHL has a function analogous to that of an F-box protein, namely, to recruit substrates to a ubiquitination machine. These results strengthen the link between overaccumulation of HIF and development of VHL disease.
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structure of the vhl elonginc elonginb complex implications for vhl tumor suppressor function
Science, 1999Co-Authors: Charles E Stebbins, William G. Kaelin, Nikola P PavletichAbstract:Mutation of the VHL tumor suppressor is associated with the inherited von Hippel–Lindau (VHL) Cancer Syndrome and the majority of kidney Cancers. VHL binds the ElonginC-ElonginB complex and regulates levels of hypoxia-inducible proteins. The structure of the ternary complex at 2.7 angstrom resolution shows two interfaces, one between VHL and ElonginC and another between ElonginC and ElonginB. Tumorigenic mutations frequently occur in a 35-residue domain of VHL responsible for ElonginC binding. A mutational patch on a separate domain of VHL indicates a second macromolecular binding site. The structure extends the similarities to the SCF (Skp1-Cul1–F-box protein) complex that targets proteins for degradation, supporting the hypothesis that VHL may function in an analogous pathway.
Hong Duk Youn - One of the best experts on this subject based on the ideXlab platform.
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p53 stabilization and transactivation by a von hippel lindau protein
Molecular Cell, 2006Co-Authors: Jae Seok Roe, Hyungsoo Kim, Soon Min Lee, Sung Tae Kim, Eun Jung Cho, Hong Duk YounAbstract:von Hippel-Lindau (VHL) disease is a rare autosomal dominant Cancer Syndrome. Although hypoxia-inducible factor-alpha (HIFalpha) is a well-documented substrate of von Hippel-Lindau tumor suppressor protein (pVHL), it remains unclear whether the dysregulation of HIF is sufficient to account for de novo tumorigenesis in VHL-deleted cells. Here we found that pVHL directly associates with and stabilizes p53 by suppressing Mdm2-mediated ubiquitination and nuclear export of p53. Moreover, upon genotoxic stress, pVHL invoked an interaction between p53 and p300 and the acetylation of p53, which ultimately led to an increase in p53 transcriptional activity and p53-mediated cell cycle arrest and apoptosis. These results suggest that the tumor suppressor pVHL has an unexpected function to upregulate the tumor suppressor p53.
Andre Roy - One of the best experts on this subject based on the ideXlab platform.
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carcinoid tumor of the common bile duct a rare complication of von hippel lindau Syndrome
World Journal of Gastroenterology, 2008Co-Authors: Otmane Nafidi, Bich Nguyen, Andre RoyAbstract:Von Hippel-Lindau Syndrome (VHL) is a rare autosomal-dominant, inherited familial Cancer Syndrome. Hemangioblastomas, pheochromocytomas and renal carcinoma are the frequent reported VHL tumors. Neuroendocrine tumors have also been described, mostly in the pancreas and rarely in the biliary trees. We report the second case of bile duct carcinoid in a 31-year-old VHL woman. She underwent right adrenalectomy for a pheochromocytoma in the past. She also had a positive family history of phenotypic expression of VHL Syndrome. The patient presented with biliary colic. Endoscopic retrograde cholangio-pancreatography showed intra-luminal bile duct mass. Surgical exploration identified a beige nodular lesion that was a carcinoid tumor on histology. This new association should be clarified by further genetic investigations.
Taeyou Kim - One of the best experts on this subject based on the ideXlab platform.
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ubiquitination of hypoxia inducible factor requires direct binding to the β domain of the von hippel lindau protein
Nature Cell Biology, 2000Co-Authors: Michael Ohh, Nikola P Pavletich, Cheol Won Park, Mircea Ivan, Michael A Hoffman, Taeyou Kim, Eric L HuangAbstract:von Hippel-Lindau (VHL) disease is a hereditary Cancer Syndrome that is characterized by the development of multiple vascular tumors and is caused by inactivation of the von Hippel-Lindau protein (pVHL). Here we show that pVHL, through its beta-domain, binds directly to hypoxia-inducible factor (HIF), thereby targeting HIF for ubiquitination in an alpha-domain-dependent manner. This is the first function to be ascribed to the pVHL beta-domain. Furthermore, we provide the first direct evidence that pVHL has a function analogous to that of an F-box protein, namely, to recruit substrates to a ubiquitination machine. These results strengthen the link between overaccumulation of HIF and development of VHL disease.
Cheol Won Park - One of the best experts on this subject based on the ideXlab platform.
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ubiquitination of hypoxia inducible factor requires direct binding to the β domain of the von hippel lindau protein
Nature Cell Biology, 2000Co-Authors: Michael Ohh, Nikola P Pavletich, Cheol Won Park, Mircea Ivan, Michael A Hoffman, Taeyou Kim, Eric L HuangAbstract:von Hippel-Lindau (VHL) disease is a hereditary Cancer Syndrome that is characterized by the development of multiple vascular tumors and is caused by inactivation of the von Hippel-Lindau protein (pVHL). Here we show that pVHL, through its beta-domain, binds directly to hypoxia-inducible factor (HIF), thereby targeting HIF for ubiquitination in an alpha-domain-dependent manner. This is the first function to be ascribed to the pVHL beta-domain. Furthermore, we provide the first direct evidence that pVHL has a function analogous to that of an F-box protein, namely, to recruit substrates to a ubiquitination machine. These results strengthen the link between overaccumulation of HIF and development of VHL disease.
