fumarate hydratase

Summary

Summary: An enzyme that catalyzes the reversible hydration of fumaric acid to yield L-malic acid. It is one of the citric acid cycle enzymes. EC 4.2.1.2.

Top Publications

  1. ncbi Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer
    Ian P M Tomlinson
    Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44, Lincoln s Inn Fields, London WC2A 3PX, UK
    Nat Genet 30:406-10. 2002
  2. ncbi Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase
    Christian Frezza
    Cancer Research UK, Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, UK
    Nature 477:225-8. 2011
  3. pmc The genetic basis of kidney cancer: a metabolic disease
    W Marston Linehan
    Urologic Oncology Branch, National Cancer Institute, Bethesda, MD 20892 1107, USA
    Nat Rev Urol 7:277-85. 2010
  4. ncbi Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer
    A King
    Cancer Research UK, The Beatson Institute for Cancer Research, Glasgow, UK
    Oncogene 25:4675-82. 2006
  5. ncbi An antioxidant response phenotype shared between hereditary and sporadic type 2 papillary renal cell carcinoma
    Aikseng Ooi
    Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA
    Cancer Cell 20:511-23. 2011
  6. pmc Fumarate hydratase deficiency in renal cancer induces glycolytic addiction and hypoxia-inducible transcription factor 1alpha stabilization by glucose-dependent generation of reactive oxygen species
    Sunil Sudarshan
    Urologic Oncology Branch, National Cancer Institute NIH, Bethesda, MD 20892, USA
    Mol Cell Biol 29:4080-90. 2009
  7. pmc Molecular genetic analysis of FIH-1, FH, and SDHB candidate tumour suppressor genes in renal cell carcinoma
    M R Morris
    Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham, The Medical School, Birmingham B15 2TT, UK
    J Clin Pathol 57:706-11. 2004
  8. pmc Renal cyst formation in Fh1-deficient mice is independent of the Hif/Phd pathway: roles for fumarate in KEAP1 succination and Nrf2 signaling
    Julie Adam
    Nuffield Department of Medicine, Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, UK
    Cancer Cell 20:524-37. 2011
  9. ncbi Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF
    Peppi Koivunen
    Collagen Research Unit, Biocenter Oulu, Departments of Medical Biochemistry and Molecular Biology and Neurology, University of Oulu, FIN 90014 Oulu, Finland
    J Biol Chem 282:4524-32. 2007
  10. pmc Inborn and acquired metabolic defects in cancer
    Christian Frezza
    Cancer Research UK, The Beatson Institute for Cancer Research, Glasgow, UK
    J Mol Med (Berl) 89:213-20. 2011

Detail Information

Publications196 found, 100 shown here

  1. ncbi Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer
    Ian P M Tomlinson
    Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44, Lincoln s Inn Fields, London WC2A 3PX, UK
    Nat Genet 30:406-10. 2002
    ..individuals with germline mutations and screening known and predicted transcripts, that this gene encodes fumarate hydratase, an enzyme of the tricarboxylic acid cycle...
  2. ncbi Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase
    Christian Frezza
    Cancer Research UK, Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, UK
    Nature 477:225-8. 2011
    b>Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC)...
  3. pmc The genetic basis of kidney cancer: a metabolic disease
    W Marston Linehan
    Urologic Oncology Branch, National Cancer Institute, Bethesda, MD 20892 1107, USA
    Nat Rev Urol 7:277-85. 2010
    ..Targeting the fundamental metabolic abnormalities in kidney cancer provides a unique opportunity for the development of more-effective forms of therapy for this disease...
  4. ncbi Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer
    A King
    Cancer Research UK, The Beatson Institute for Cancer Research, Glasgow, UK
    Oncogene 25:4675-82. 2006
    ..enhanced glycolysis in tumours was supplied by the recent discovery that succinate dehydrogenase (SDH) and fumarate hydratase (FH) are tumour suppressors and which associated, for the first time, mitochondrial enzymes and their ..
  5. ncbi An antioxidant response phenotype shared between hereditary and sporadic type 2 papillary renal cell carcinoma
    Aikseng Ooi
    Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA
    Cancer Cell 20:511-23. 2011
    b>Fumarate hydratase (FH) mutation causes hereditary type 2 papillary renal cell carcinoma (PRCC2). The main effect of FH mutation is fumarate accumulation...
  6. pmc Fumarate hydratase deficiency in renal cancer induces glycolytic addiction and hypoxia-inducible transcription factor 1alpha stabilization by glucose-dependent generation of reactive oxygen species
    Sunil Sudarshan
    Urologic Oncology Branch, National Cancer Institute NIH, Bethesda, MD 20892, USA
    Mol Cell Biol 29:4080-90. 2009
    ..cancer syndrome linked to biallelic inactivation of the gene encoding the tricarboxylic acid cycle enzyme fumarate hydratase (FH)...
  7. pmc Molecular genetic analysis of FIH-1, FH, and SDHB candidate tumour suppressor genes in renal cell carcinoma
    M R Morris
    Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham, The Medical School, Birmingham B15 2TT, UK
    J Clin Pathol 57:706-11. 2004
    ..In RCC, three candidate HIF activating genes exist-FIH-1 (factor inhibiting HIF), SDHB, and FH-which may be dependent or independent of VHL inactivation...
  8. pmc Renal cyst formation in Fh1-deficient mice is independent of the Hif/Phd pathway: roles for fumarate in KEAP1 succination and Nrf2 signaling
    Julie Adam
    Nuffield Department of Medicine, Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, UK
    Cancer Cell 20:524-37. 2011
    The Krebs cycle enzyme fumarate hydratase (FH) is a human tumor suppressor whose inactivation is associated with the development of leiomyomata, renal cysts, and tumors...
  9. ncbi Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF
    Peppi Koivunen
    Collagen Research Unit, Biocenter Oulu, Departments of Medical Biochemistry and Molecular Biology and Neurology, University of Oulu, FIN 90014 Oulu, Finland
    J Biol Chem 282:4524-32. 2007
    ..Similar, although much smaller, changes were found in cultured fibroblasts from a patient with fumarate hydratase (FH) deficiency and upon silencing FH using small interfering RNA...
  10. pmc Inborn and acquired metabolic defects in cancer
    Christian Frezza
    Cancer Research UK, The Beatson Institute for Cancer Research, Glasgow, UK
    J Mol Med (Berl) 89:213-20. 2011
    ....
  11. ncbi High growth rate downregulates fumA mRNA transcription but is dramatically compensated by its mRNA stability in Escherichia coli
    Hsiao Hsien Lin
    Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsinchu 30050, Taiwan, ROC
    Curr Microbiol 64:412-7. 2012
    ..This notion indicates that mRNA stability plays an essential role in maintaining a critical cellular level of a given protein when the mRNA transcript is downregulated by a metabolic event...
  12. ncbi Molecular pathways: Fumarate hydratase-deficient kidney cancer--targeting the Warburg effect in cancer
    W Marston Linehan
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Clin Cancer Res 19:3345-52. 2013
    ..HLRCC is characterized by germline mutation of the tricarboxylic acid (TCA) cycle enzyme, fumarate hydratase (FH)...
  13. ncbi Clinical features of multiple cutaneous and uterine leiomyomatosis: an underdiagnosed tumor syndrome
    N Afrina Alam
    Molecular and Population Genetics Laboratory, Cancer Research UK, London
    Arch Dermatol 141:199-206. 2005
    ..To investigate the clinical features of the multiple cutaneous and uterine leiomyomatosis (MCUL) syndrome, including the hereditary leiomyomatosis and renal cell cancer syndrome...
  14. ncbi Fumarase: a paradigm of dual targeting and dual localized functions
    Ohad Yogev
    Department of Microbiology and Molecular Genetics, IMRIC, Faculty of Medicine, Hebrew University, Jerusalem, Israel
    FEBS J 278:4230-42. 2011
    ..Strikingly, upon DNA damage the protein is transported from the cytosol to the nucleus, where by virtue of its enzymatic activity it participates in the DNA damage response...
  15. ncbi Dual localization of fumarase is dependent on the integrity of the glyoxylate shunt
    Neta Regev-Rudzki
    Department of Microbiology and Molecular Genetics, IMRIC, Faculty of Medicine, The Hebrew University, Jerusalem, Israel
    Mol Microbiol 72:297-306. 2009
    ..Specifically, we suggest that metabolites of the glyoxylate shunt act as 'nanosensors' for fumarase subcellular targeting and distribution. The possible mechanisms involved are discussed...
  16. pmc Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer
    M H Wei
    Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892, USA
    J Med Genet 43:18-27. 2006
    ..smooth muscle tumours of the skin and uterus and/or renal cancer and is associated with mutations in the fumarate hydratase gene (FH)...
  17. pmc The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency
    Jean Pierre Bayley
    Department of Human Genetics, Leiden University Medical Center, P, O, Box 9503, 2300 RA, Leiden, The Netherlands
    BMC Med Genet 9:20. 2008
    b>Fumarate hydratase (HGNC approved gene symbol - FH), also known as fumarase, is an enzyme of the tricarboxylic acid (TCA) cycle, involved in fundamental cellular energy production...
  18. pmc Fumarase: a mitochondrial metabolic enzyme and a cytosolic/nuclear component of the DNA damage response
    Ohad Yogev
    Department of Microbiology and Molecular Genetics, IMRIC, Faculty of Medicine, Hebrew University, Jerusalem, Israel
    PLoS Biol 8:e1000328. 2010
    ..This study shows an exciting crosstalk between primary metabolism and the DNA damage response, thereby providing a scenario for metabolic control of tumor propagation...
  19. ncbi Anaerobic growth of Escherichia coli on D-tartrate depends on the fumarate carrier DcuB and fumarase, rather than the L-tartrate carrier TtdT and L-tartrate dehydratase
    Ok Bin Kim
    Institut für Mikrobiologie und Weinforschung, Universitat Mainz, Becherweg 15, 55099 Mainz, Germany
    Arch Microbiol 188:583-9. 2007
    ..No D-tartrate specific carriers and enzymes are involved in the pathway...
  20. ncbi Targeted inactivation of fh1 causes proliferative renal cyst development and activation of the hypoxia pathway
    Patrick J Pollard
    Molecular and Population Genetics Laboratory, Histopathology Department, London Research Institute, Cancer Research UK, Hammersmith Hospital, Imperial College London, United Kingdom
    Cancer Cell 11:311-9. 2007
    Germline mutations in the fumarate hydratase (FH) tumor suppressor gene predispose to leiomyomatosis, renal cysts, and renal cell cancer (HLRCC). HLRCC tumors overexpress HIF1alpha and hypoxia pathway genes...
  21. ncbi Regulatory role of cAMP receptor protein over Escherichia coli fumarase genes
    Yu Pei Chen
    Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, 300, Taiwan
    J Microbiol 50:426-33. 2012
    ..In addition, Fnr was confirmed as a repressor of fumC for the first time. This study elucidates the effects of Crp on fumarase gene expression...
  22. pmc Inhibition of mitochondrial aconitase by succination in fumarate hydratase deficiency
    Nicola Ternette
    Central Proteomics Facility, Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, UK
    Cell Rep 3:689-700. 2013
    The gene encoding the Krebs cycle enzyme fumarate hydratase (FH) is mutated in hereditary leiomyomatosis and renal cell cancer (HLRCC)...
  23. pmc The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels
    Wing Hang Tong
    Molecular Medicine Program, Eunice Kennedy Shriver National Institute of Child Health and Development, Bethesda, Maryland, USA
    Cancer Cell 20:315-27. 2011
    Inactivation of the TCA cycle enzyme, fumarate hydratase (FH), drives a metabolic shift to aerobic glycolysis in FH-deficient kidney tumors and cell lines from patients with hereditary leiomyomatosis renal cell cancer (HLRCC), resulting ..
  24. ncbi Novel FH mutations in families with hereditary leiomyomatosis and renal cell cancer (HLRCC) and patients with isolated type 2 papillary renal cell carcinoma
    Betty Gardie
    Génétique Oncologique EPHE, INSERM U753, Institut de cancérologie Gustave Roussy Villejuif, Faculte de Medecine Paris Sud, 63 avenue du Général Leclerc, 94276 Le Kremlin Bicetre, France
    J Med Genet 48:226-34. 2011
    ..HLRCC results from heterozygous germline mutations in the tumour suppressor fumarate hydratase (FH) gene.
  25. ncbi Hereditary leiomyomatosis and renal cell cancer: update on clinical and molecular characteristics
    Heli J Lehtonen
    Department of Medical Genetics, Genome Scale Biology Research Program, Biomedicum Helsinki, Haartman Institute, University of Helsinki, Haartmaninkatu 8, P O Box 63, Helsinki 00290, Finland
    Fam Cancer 10:397-411. 2011
    ..To date inactivating heterozygous mutations in the fumarate hydratase (FH, fumarase) gene, predisposing to HLRCC, have been found in approximately 180 families worldwide...
  26. pmc UOK 262 cell line, fumarate hydratase deficient (FH-/FH-) hereditary leiomyomatosis renal cell carcinoma: in vitro and in vivo model of an aberrant energy metabolic pathway in human cancer
    Youfeng Yang
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Dr, MSC 1107, Bldg 10 CRC, Room 1 5942, Bethesda, MD 20892 1107
    Cancer Genet Cytogenet 196:45-55. 2010
    ..carcinoma (HLRCC) is an aggressive form of RCC characterized by germline mutation of the Krebs cycle enzyme fumarate hydratase (FH), and one known to be highly metastatic and unusually lethal...
  27. pmc Production of hyperpolarized [1,4-13C2]malate from [1,4-13C2]fumarate is a marker of cell necrosis and treatment response in tumors
    Ferdia A Gallagher
    Cancer Research United Kingdom, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, United Kingdom
    Proc Natl Acad Sci U S A 106:19801-6. 2009
    ..Given that fumarate is an endogenous molecule, this technique has the potential to be used clinically...
  28. ncbi Familial multiple cutaneous and uterine leiomyomas associated with papillary renal cell cancer
    I Chan
    Genetic Skin Disease Group, St John s Institute of Dermatology, The Guy s, King s and St Thomas Medical School, St Thomas Hospital, London, UK
    Clin Exp Dermatol 30:75-8. 2005
    ..Recently, heterozygous mutations in the gene encoding fumarate hydratase have been found to underlie both conditions...
  29. pmc A metabolic model of the mitochondrion and its use in modelling diseases of the tricarboxylic acid cycle
    Anthony C Smith
    The Medical Research Council, Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK
    BMC Syst Biol 5:102. 2011
    ..To understand how mitochondrial metabolic dysfunction contributes to these diseases, a metabolic model of a human heart mitochondrion was created...
  30. ncbi The TCA cycle and tumorigenesis: the examples of fumarate hydratase and succinate dehydrogenase
    Patrick J Pollard
    Molecular and Population Genetics Laboratory, Cancer Research UK, Lincoln s Inn Fields, London, UK
    Ann Med 35:632-9. 2003
    ..The two enzymes, fumarate hydratase (FH) and succinate dehydrogenase (SDH), are ubiquitously expressed, playing a vital role in adenosine ..
  31. ncbi Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis
    Houman Ashrafian
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Headington, United Kingdom
    Cancer Res 70:9153-65. 2010
    Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by mutations in the Krebs cycle enzyme fumarate hydratase (FH)...
  32. ncbi Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency
    N A Alam
    Molecular and Population Genetics Laboratory, Cancer Research UK, Lincoln s Inn Fields, London WC2A 3PX, UK
    Hum Mol Genet 12:1241-52. 2003
    Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL)...
  33. ncbi Aberrant succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a robust biomarker of mutation status
    Chiara Bardella
    Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, UK
    J Pathol 225:4-11. 2011
    Germline mutations in the FH gene encoding the Krebs cycle enzyme fumarate hydratase predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome...
  34. ncbi Differential metabolic consequences of fumarate hydratase and respiratory chain defects
    Nuno Raimundo
    Program of Molecular Neurology Biomedicum Helsinki, Finland
    Biochim Biophys Acta 1782:287-94. 2008
    ..A key enzyme of tricarboxylic cycle, fumarate hydratase (FH), is involved in encephalopathies, but also in leiomyoma formation, and occasionally also in various ..
  35. ncbi Regulation of fumarase (fumB) gene expression in Escherichia coli in response to oxygen, iron and heme availability: role of the arcA, fur, and hemA gene products
    C P Tseng
    Institute of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, ROC
    FEMS Microbiol Lett 157:67-72. 1997
    ..In addition, fumB-lacZ expression was shown to vary depending on the DNA superhelicity. This study further delineates the regulation of the fumB gene in cell growth...
  36. ncbi Pseudohypoxic pathways in renal cell carcinoma
    Gennady Bratslavsky
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892 1107, USA
    Clin Cancer Res 13:4667-71. 2007
    Mutations of the von Hippel-Lindau (VHL) or fumarate hydratase (FH) genes lead to morphologically different renal cell carcinomas with distinct clinical courses and outcomes...
  37. ncbi Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations
    P J Pollard
    Molecular and Population Genetics Laboratory, London WC2A 3PX, UK
    Hum Mol Genet 14:2231-9. 2005
    The nuclear-encoded Krebs cycle enzymes, fumarate hydratase (FH) and succinate dehydrogenase (SDHB, -C and -D), act as tumour suppressors...
  38. ncbi SDH5 mutations and familial paraganglioma: somewhere Warburg is smiling
    William G Kaelin
    Howard Hughes Medical Institute, Dana Farber Cancer Institute and Brigham and Women s Hospital, Boston, MA 02115, USA
    Cancer Cell 16:180-2. 2009
    ..Moreover, they detected SDH5 mutations in a large kindred with familial paraganglioma...
  39. ncbi Clinical and molecular genetic aspects of hereditary multiple cutaneous leiomyomatosis
    Sadhanna Badeloe
    Department of Dermatology and Maastricht University Center for Molecular Dermatology and GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands
    Eur J Dermatol 19:545-51. 2009
    ..All disease variants result from heterozygous mutations in the fumarate hydratase (FH) gene. Cutaneous leiomyoma can easily be recognized and confirmed by histological examination...
  40. pmc Fumarate hydratase enzyme activity in lymphoblastoid cells and fibroblasts of individuals in families with hereditary leiomyomatosis and renal cell cancer
    M Pithukpakorn
    J Med Genet 43:755-62. 2006
    ..Hereditary leiomyomatosis and renal cell cancer (HLRCC) is the autosomal dominant heritable syndrome with predisposition to development of renal cell carcinoma and smooth muscle tumours of the skin and uterus...
  41. ncbi Mitochondrial import of human and yeast fumarase in live mammalian cells: retrograde translocation of the yeast enzyme is mainly caused by its poor targeting sequence
    Bhag Singh
    Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada L8N 3Z5
    Biochem Biophys Res Commun 346:911-8. 2006
    ....
  42. ncbi Strong family history of uterine leiomyomatosis warrants fumarate hydratase mutation screening
    Jaana Tolvanen
    Department of Medical Genetics, Genome Scale Biology Research Program, University of Helsinki, Helsinki, Finland
    Hum Reprod 27:1865-9. 2012
    ..HLRCC is caused by heterozygous germline mutations in the fumarate hydratase (FH) gene...
  43. pmc Fumarate hydratase inactivation in renal tumors: HIF1α, NRF2, and "cryptic targets" of transcription factors
    Aikseng Ooi
    Laboratory of Interdisciplinary Urological Oncology, Van Andel Research Institute, 333 Bostwick Ave NE, Grand Rapids, MI 49503, USA
    Chin J Cancer 31:413-20. 2012
    Biallelic inactivation of fumarate hydratase(FH) causes type 2 papillary renal cell carcinoma (PRCC2), uterine fibroids, and cutaneous leimyomas, a condition known as hereditary leiomyomatosis and renal cell cancer(HLRCC)...
  44. ncbi Purification and characterization of two types of fumarase from Escherichia coli
    Y Ueda
    Department of Chemistry, Faculty of Science, Kyoto University
    J Biochem 109:728-33. 1991
    ..FUMC was stable, Fe-independent and quite similar to mammalian fumarases in enzymatic properties...
  45. ncbi Cerebral cavernomas in a family with multiple cutaneous and uterine leiomyomas associated with a new mutation in the fumarate hydratase gene
    Elena Campione
    J Invest Dermatol 127:2271-3. 2007
  46. ncbi A two-dimensional screen for AMPK substrates identifies tumor suppressor fumarate hydratase as a preferential AMPKα2 substrate
    Anna Klaus
    Laboratory of Fundamental and Applied Bioenergetics, University Joseph Fourier, Grenoble Cedex 9, France
    J Proteomics 75:3304-13. 2012
    ..of this screen to full-length AMPK α2β2γ1 and soluble rat liver proteins identified the tumor suppressor fumarate hydratase (FH)...
  47. pmc Nucleotide sequence of the FNR-regulated fumarase gene (fumB) of Escherichia coli K-12
    P J Bell
    Department of Microbiology, University of Sheffield, United Kingdom
    J Bacteriol 171:3494-503. 1989
    ....
  48. pmc Structural basis of fumarate hydratase deficiency
    Sarah Picaud
    Structural Genomics Consortium, University of Oxford, Old Road Campus, Headington OX3 7DQ, UK
    J Inherit Metab Dis 34:671-6. 2011
    b>Fumarate hydratase catalyzes the stereospecific hydration across the olefinic double bond in fumarate leading to L-malate...
  49. ncbi No evidence for epigenetic inactivation of fumarate hydratase in leiomyomas and leiomyosarcomas
    Karen T Barker
    Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Cancer Lett 235:136-40. 2006
    Germline mutations in Fumarate Hydratase (FH) cause the development of leiomyomas and leiomyosarcomas in the syndromes Multiple Cutaneous and Uterine Leiomyomata (MCUL1) and Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)...
  50. pmc Reduced expression of fumarate hydratase in clear cell renal cancer mediates HIF-2α accumulation and promotes migration and invasion
    Sunil Sudarshan
    Department of Urology, University of Texas Health Sciences Center at San Antonio, Texas, United States of America
    PLoS ONE 6:e21037. 2011
    Germline mutations of FH, the gene that encodes for the tricarboxylic acid TCA (TCA) cycle enzyme fumarate hydratase, are associated with an inherited form of cancer referred to as Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)...
  51. ncbi Involvement of fumarate hydratase in nonsyndromic uterine leiomyomas: genetic linkage analysis and FISH studies
    Karen L Gross
    Department of Pathology, University of Vermont, Burlington, Vermont, USA
    Genes Chromosomes Cancer 41:183-90. 2004
    Recently, germline mutations of the fumarate hydratase (FH) gene, in 1q42.1, have been found to be involved in syndromes associated with uterine leiomyomas (ULs)...
  52. pmc A novel fumarate hydratase-deficient HLRCC kidney cancer cell line, UOK268: a model of the Warburg effect in cancer
    Youfeng Yang
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    Cancer Genet 205:377-90. 2012
    ..and renal cell carcinoma (HLRCC) is an aggressive form of RCC characterized by germline mutation of fumarate hydratase (FH), followed by somatic loss of the remaining wild-type allele and known to be a highly metastatic and ..
  53. pmc Cloning, mapping, and expression of the fumarase gene of Escherichia coli K-12
    J R Guest
    J Bacteriol 153:588-96. 1983
    ..The basis for the complementation by fumB was not defined...
  54. ncbi The genetic and metabolic signature of oncocytic transformation implicates HIF1alpha destabilization
    Anna Maria Porcelli
    Dipartimento di Biologia Evoluzionistica Sperimentale, Universita di Bologna, Bologna 40126, Italy
    Hum Mol Genet 19:1019-32. 2010
    ....
  55. ncbi Multiple cutaneous and uterine leiomyomata resulting from missense mutations in the fumarate hydratase gene
    G S Chuang
    Department of Dermatology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA
    Clin Exp Dermatol 31:118-21. 2006
    ..3-43 and subsequently, germline mutations in the fumarate hydratase (FH) gene have been identified...
  56. doi Hereditary multiple cutaneous leiomyoma resulting from novel mutations in the fumarate hydratase gene
    Sadhanna Badeloe
    J Dermatol Sci 51:139-43. 2008
  57. ncbi Mutation screening of fumarate hydratase by multiplex ligation-dependent probe amplification: detection of exonic deletion in a patient with leiomyomatosis and renal cell cancer
    Taru Ahvenainen
    Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, PO Box 63, FI 00014 Helsinki, Finland
    Cancer Genet Cytogenet 183:83-8. 2008
    ..Heterozygous germline mutations in the fumarate hydratase (FH, fumarase) gene are known to cause HLRCC...
  58. ncbi A novel missense mutation in fumarate hydratase in an Italian patient with a diffuse variant of cutaneous leiomyomatosis (Reed's syndrome)
    F Rongioletti
    Section of Dermatology, DISEM, University of Genoa, Genoa, Italy
    Dermatology 221:378-80. 2010
    ..This syndrome overlaps with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome...
  59. ncbi The mitochondrial targeting sequence tilts the balance between mitochondrial and cytosolic dual localization
    Neta Regev-Rudzki
    Department of Molecular Biology, Hebrew University Medical School, Jerusalem, Israel
    J Cell Sci 121:2423-31. 2008
    ..Our results suggest that the translocation rate and folding of proteins during import into mitochondria determines the extent to which molecules are withdrawn back into the cytosol...
  60. ncbi Translation-coupled translocation of yeast fumarase into mitochondria in vivo
    Ohad Yogev
    Department of Molecular Biology, Hebrew University Medical School, Jerusalem 91120, Israel
    J Biol Chem 282:29222-9. 2007
    ....
  61. ncbi Hereditary leiomyomatosis and renal cell cancer in families referred for fumarate hydratase germline mutation analysis
    D L Smit
    Department of Clinical Genetics, VU University Medical Centre, Amsterdam, The Netherlands
    Clin Genet 79:49-59. 2011
    Heterozygous fumarate hydratase (FH) germline mutations cause hereditary leiomyomatosis and renal cell cancer (HLRCC), an autosomal dominant syndrome characterized by multiple cutaneous piloleiomyomas, uterine leiomyomas and papillary ..
  62. ncbi The cytosolic pathway of L-malic acid synthesis in Saccharomyces cerevisiae: the role of fumarase
    O Pines
    Department of Molecular Biology, Hebrew University Hadassah Medical School, Jerusalem, Israel
    Appl Microbiol Biotechnol 46:393-9. 1996
    ..b) Overexpression of cytosolic fumarase does not cause accumulation of fumaric acid (but rather more L-malic acid). (c) According to 13C NMR studies there is no interconversion of cytosolic L-malic and fumaric acids...
  63. ncbi Evidence for a founder effect of the germline fumarate hydratase gene mutation R58P causing hereditary leiomyomatosis and renal cell cancer (HLRCC)
    W Heinritz
    Institute of Human Genetics, University of Leipzig, Medical Faculty, Leipzig, Germany
    Ann Hum Genet 72:35-40. 2008
    ..syndrome of multiple cutaneous and uterine leiomyomas (MCUL1) and a germline missense mutation (R58P) in the fumarate hydratase gene (FH)...
  64. ncbi A novel mutation of the fumarase gene in a family with autosomal recessive fumarase deficiency
    Anne M Remes
    Department of Neurology, University of Oulu, Oulu, Finland
    J Mol Med (Berl) 82:550-4. 2004
    ..Several autosomal recessive mutations in the fumarate hydratase gene have been identified as a cause of the lack of fumarase activity in affected individuals...
  65. ncbi Fumaric aciduria: mild phenotype in a 8-year-old girl with novel mutations
    M Maradin
    Clinical Institute of Laboratory Diagnosis, University Hospital Center Zagreb, Croatia
    J Inherit Metab Dis 29:683. 2006
    Fumaric aciduria is a rare, autosomal recessive disorder caused by deficient activity of fumarate hydratase (FH). Common clinical features are hypotonia, failure to thrive, severe psychomotor retardation and seizures...
  66. ncbi Fumarase tumor suppressor gene and MET oncogene cooperate in upholding transformation and tumorigenesis
    Barbara Costa
    Department of Oncological Sciences, University of Torino School of Medicine, Turin, Italy
    FASEB J 24:2680-8. 2010
    Loss of the fumarate hydratase (FH) tumor suppressor gene results in the development of benign tumors that rarely, but regrettably, progress to very aggressive cancers...
  67. ncbi Germline fumarate hydratase mutations and evidence for a founder mutation underlying multiple cutaneous and uterine leiomyomata
    Gary S Chuang
    Department of Dermatology, Columbia University, New York, New York, USA
    J Am Acad Dermatol 52:410-6. 2005
    ..3-43 and subsequently, dominantly inherited mutations in the fumarate hydratase gene ( FH ) were identified...
  68. ncbi Distinct expression profile in fumarate-hydratase-deficient uterine fibroids
    Sakari Vanharanta
    Department of Medical Genetics, University of Helsinki, Finland
    Hum Mol Genet 15:97-103. 2006
    ..Heterozygous germline mutations in the nuclear gene encoding fumarate hydratase (FH), an enzyme catalyzing the hydration of fumarate in the Krebs tricarboxylic acid cycle, cause hereditary ..
  69. ncbi HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability
    Jennifer S Isaacs
    Urologic Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA
    Cancer Cell 8:143-53. 2005
    Individuals with hemizygous germline fumarate hydratase (FH) mutations are predisposed to renal cancer...
  70. pmc Increased risk of cancer in patients with fumarate hydratase germline mutation
    H J Lehtonen
    Department of Medical Genetics, PO Box 63 Haartmaninkatu 8, Biomedicum Helsinki, FIN 00014 University of Helsinki, Finland
    J Med Genet 43:523-6. 2006
    ..cell cancer (HLRCC) is a tumour predisposition syndrome caused by heterozygous germline mutations in the fumarate hydratase (FH) gene...
  71. pmc Biallelic inactivation of fumarate hydratase (FH) occurs in nonsyndromic uterine leiomyomas but is rare in other tumors
    Rainer Lehtonen
    Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland
    Am J Pathol 164:17-22. 2004
    Germline mutations in the fumarate hydratase (FH) gene at 1q43 predispose to dominantly inherited cutaneous and uterine leiomyomas, uterine leiomyosarcoma, and papillary renal cell cancer (HLRCC syndrome)...
  72. ncbi Inborn errors of the Krebs cycle: a group of unusual mitochondrial diseases in human
    P Rustin
    Unite de Recherches sur les Handicaps Genetiques de l Enfant, INSERM U 393, Hopital des Enfants Malades, Paris, France
    Biochim Biophys Acta 1361:185-97. 1997
    ....
  73. ncbi Molecular analysis and prenatal diagnosis of human fumarase deficiency
    E M Coughlin
    Amino Acid Disorder Laboratory, Massachusetts General Hospital, Boston 02129, USA
    Mol Genet Metab 63:254-62. 1998
    ..Seven at-risk pregnancies were monitored with one prenatal diagnosis of fumarase deficiency by molecular analysis and favorable outcome of the other pregnancies as predicted by enzyme assay of cultured fetal cells or molecular analysis...
  74. pmc Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America
    Jorge R Toro
    Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Executive Plaza South, Rockville, MD 20892, USA
    Am J Hum Genet 73:95-106. 2003
    ..Although the identification of germline mutations in the fumarate hydratase (FH) gene in European families supports it as the susceptibility gene for HLRCC, its role in families in ..
  75. ncbi Fumarate hydratase deficiency in monozygotic twins
    Tonya M Phillips
    Department of Pediatrics, Division of Neurology, University of Arkansas for Medical Sciences and Arkansas Children s Hospital, Little Rock, Arkansas, USA
    Pediatr Neurol 35:150-3. 2006
    Monozygotic twins with fumarate hydratase deficiency presenting with profound hypotonia and developmental delay are reported...
  76. ncbi Germline fumarate hydratase mutations in families with multiple cutaneous and uterine leiomyomata
    Amalia Martinez-Mir
    Department of Dermatology, Columbia University, New York, New York, USA
    J Invest Dermatol 121:741-4. 2003
    Germline mutations in the fumarate hydratase gene (FH) predispose to multiple cutaneous and uterine leiomyoma syndrome (MCL) and MCL associated with renal cell cancer...
  77. pmc Dysregulation of hypoxia pathways in fumarate hydratase-deficient cells is independent of defective mitochondrial metabolism
    Linda O'Flaherty
    Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
    Hum Mol Genet 19:3844-51. 2010
    Mutations in the gene encoding the Krebs cycle enzyme fumarate hydratase (FH) predispose to hereditary leiomyomatosis and renal cell cancer in affected individuals...
  78. ncbi Fumarate hydratase deficiency and cancer: activation of hypoxia signaling?
    Peter J Ratcliffe
    The Henry Wellcome Building for Molecular Physiology, University of Oxford, Headington Campus, Roosevelt Drive, Oxford OX3 7BN, United Kingdom
    Cancer Cell 11:303-5. 2007
    ..renal cell cancer (HLRCC) unexpectedly revealed germline defects in the gene encoding the Krebs cycle enzyme fumarate hydratase (FH), stimulating great interest in the underlying mechanism of oncogenesis...
  79. ncbi Downregulation of SRF-FOS-JUNB pathway in fumarate hydratase deficiency and in uterine leiomyomas
    N Raimundo
    Research Program of Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
    Oncogene 28:1261-73. 2009
    ..Dominant defects of fumarate hydratase (FH) result in predisposition to cutaneous and uterine leiomyomas, and renal cell cancer...
  80. ncbi Fumarase deficiency caused by homozygous P131R mutation and paternal partial isodisomy of chromosome 1
    Wen Qi Zeng
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02129, USA
    Am J Med Genet A 140:1004-9. 2006
    ..Although FD is an autosomal recessive disorder, the effects of uniparental disomy (UPD) should be considered in genetic counseling since the recurrence risk of an affected child is significantly reduced when the disorder is due to UPD...
  81. ncbi Fumarate hydratase mutations and predisposition to cutaneous leiomyomas, uterine leiomyomas and renal cancer
    N A Alam
    Molecular and Population Genetics Laboratory, Cancer Research UK, Lincoln s Inn Fields, London WC2A 3PX, UK
    Br J Dermatol 153:11-7. 2005
    Germline heterozygous loss-of-function mutations of fumarate hydratase (FH) predispose to the autosomal dominant syndrome of multiple cutaneous and uterine leiomyomatosis (MCUL)...
  82. pmc Oxygen- and growth rate-dependent regulation of Escherichia coli fumarase (FumA, FumB, and FumC) activity
    C P Tseng
    Institute of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, Republic of China
    J Bacteriol 183:461-7. 2001
    ..Therefore, synthesis of the three fumarase enzymes is controlled in a hierarchical fashion depending on the environmental oxygen that the cell encounters...
  83. ncbi Analysis of fumarate hydratase mutations in a population-based series of early onset uterine leiomyosarcoma patients
    Sanna K Ylisaukko-oja
    Department of Medical Genetics, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8, Finland
    Int J Cancer 119:283-7. 2006
    Germline mutations in fumarate hydratase (FH) gene at 1q43 predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome...
  84. ncbi Two biochemically distinct classes of fumarase in Escherichia coli
    S A Woods
    Department of Microbiology, University of Sheffield, U K
    Biochim Biophys Acta 954:14-26. 1988
    ..Apart from one region containing a Gly-Ser-X-X-Met-X-X-Lys-X-Asn consensus sequence, no significant homology was detected between the Class I and Class II fumarases...
  85. ncbi Deficiency of mitochondrial fumarase activity in tomato plants impairs photosynthesis via an effect on stomatal function
    Adriano Nunes-Nesi
    Max Planck Institut fur Molekulare Pflanzenphysiologie, Am Muhlenberg 1, 14476 Golm, Germany
    Plant J 50:1093-106. 2007
    Transgenic tomato (Solanum lycopersicum) plants expressing a fragment of a fumarate hydratase (fumarase) gene in the antisense orientation and exhibiting considerable reductions in the mitochondrial activity of this enzyme show impaired ..
  86. ncbi MmcBC in Pelotomaculum thermopropionicum represents a novel group of prokaryotic fumarases
    Takefumi Shimoyama
    Marine Biotechnology Institute, Heita, Kamaishi, Iwate, Japan
    FEMS Microbiol Lett 270:207-13. 2007
    ..Its molecular size was 64.2 kDa, indicating that it consisted of one MmcB and one MmcC. EPR spectra revealed that it had an oxygen-sensitive [4Fe-4S] cluster. We propose that MmcBC represents a novel group of prokaryotic fumarases...
  87. ncbi Biochemical and molecular characterization of fumarase from plants: purification and characterization of the enzyme--cloning, sequencing, and expression of the gene
    R H Behal
    Department of Botany, Iowa State University, Ames 50011, USA
    Arch Biochem Biophys 348:65-74. 1997
    ..Adenylates were highly inhibitory; the degree of this inhibition was reduced in the presence of Mg2+, suggesting that uncomplexed adenylates are the inhibitory species...
  88. ncbi Mitochondria, from cell death to proliferation
    Pierre Rustin
    Nat Genet 30:352-3. 2002
  89. ncbi Identification of two [4Fe-4S]-cluster-containing hydro-lyases from Pyrococcus furiosus
    Barbara M A van Vugt-Lussenburg
    Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft, The Netherlands
    Microbiology 155:3015-20. 2009
    ..Aconitase probably plays a role in amino acid synthesis when the organism grows on carbohydrates. However, the function of the seemingly metabolically isolated fumarase in Pyr. furiosus has yet to be established...
  90. pmc Novel role of fumarate metabolism in dahl-salt sensitive hypertension
    Zhongmin Tian
    Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    Hypertension 54:255-60. 2009
    ..These data suggest a novel role for fumarate metabolism in salt-induced hypertension and renal medullary oxidative stress...
  91. ncbi Expression profiling identifies a novel alpha-methylacyl-CoA racemase exon with fumarate hydratase homology
    Grace L Shen-Ong
    Gene Logic Inc, Gaithersburg, Maryland 20878, USA
    Cancer Res 63:3296-301. 2003
    ..from an alternatively spliced exon with 88% identity to a 521-bp sequence that spans four exons of the fumarate hydratase. The predicted protein sequence revealed a novel GLGELIL peptide shared by both proteins...
  92. pmc Decreased mitochondrial activities of malate dehydrogenase and fumarase in tomato lead to altered root growth and architecture via diverse mechanisms
    Margaretha J van der Merwe
    Max Planck Institute of Molecular Plant Physiology, D 14476 Potsdam Golm, Germany
    Plant Physiol 149:653-69. 2009
    ..These data are discussed in the context of current models of root growth and biomass partitioning...
  93. ncbi Mitochondrial and cytosolic isoforms of yeast fumarase are derivatives of a single translation product and have identical amino termini
    E Sass
    Department of Molecular Biology, Hebrew University Medical School, Jerusalem 91120, Israel
    J Biol Chem 276:46111-7. 2001
    ....
  94. ncbi A cancer-predisposing "hot spot" mutation of the fumarase gene creates a dominant negative protein
    Annalisa Lorenzato
    Laboratory of Cancer Genetics, Institute for Cancer Research and Treatment IRCC, University of Turin Medical School, SP142, KM 395, 10060 Candiolo, Turin, Italy
    Int J Cancer 122:947-51. 2008
    The Fumarase (Fumarate Hydratase, FH) is a tumor suppressor gene whose germline heterozygous mutations predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC)...
  95. ncbi Folding of fumarase during mitochondrial import determines its dual targeting in yeast
    Ehud Sass
    Department of Molecular Biology, Hebrew University Medical School, Jerusalem 91120, Israel
    J Biol Chem 278:45109-16. 2003
    ....
  96. pmc The role of the allosteric B site in the fumarase reaction
    Irwin A Rose
    Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 101:3393-7. 2004
    ..It is proposed that the "extra" malate represents a stage in the transfer of substrate and product between the solvent and the "buried" active site of the enzyme...
  97. pmc X-ray crystallographic and kinetic correlation of a clinically observed human fumarase mutation
    Marcel Estevez
    Johns Hopkins University, School of Medicine, Department of Neuroscience, Baltimore, Maryland 21205, USA
    Protein Sci 11:1552-7. 2002
    ..Subsequent kinetic and X-ray crystal structure analyses show changes in the turnover number and the cocrystal structure with bound citrate...
  98. ncbi Molecular basis for thermal properties of Streptomyces thermovulgaris fumarase C hinge at hydrophilic amino acids R163, E170 and S347
    Wenjie Lin
    Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore, 117597, Singapore
    Appl Microbiol Biotechnol 75:329-35. 2007
    ..These findings support stFUMC as a highly efficient, thermostable fumarase C with industrial potential and suggest that R163, E170 and S347 are involved in the enhancement of thermal properties in fumarase C...
  99. pmc Mutations of fumarase that distinguish between the active site and a nearby dicarboxylic acid binding site
    T Weaver
    Department of Biochemistry, University of Minnesota, Minneapolis 55455, USA
    Protein Sci 6:834-42. 1997
    ..In the H188N mutation at the active site, the new asparagine side chain still interacts with an active site water that appears to have moved slightly as a result of the mutation...
  100. ncbi The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome
    Maria J Merino
    Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Am J Surg Pathol 31:1578-85. 2007
    ..The mutation of this condition has been identified in the fumarate hydratase (FH, 1q42.3-q43) gene...
  101. ncbi Tricarboxylic acid cycle dysfunction as a cause of human diseases and tumor formation
    Jean Jacques Briere
    Institut National de la Santé et de la Recherche Médicale INSERM Unité 676, Hopital Robert Debre, Paris
    Am J Physiol Cell Physiol 291:C1114-20. 2006
    ....

Research Grants14

  1. Role of fumarate hydratase in renal hypoxia and tumorigenesis
    Sunil Sudarshan; Fiscal Year: 2013
    ..cancer linked to germline mutations of the FH gene which encodes the tricarboxylic acid (TCA) cycle enzyme fumarate hydratase. HLRCC kidney cancers are remarkable for their biologic aggressiveness...
  2. Mechanisms of Metabolic Gene Mutations in Cancer
    Yue Xiong; Fiscal Year: 2013
    ..genes encoding for four different metabolic enzymes are frequently mutated in human cancer, including fumarate hydratase (FH), succinate gehygrogenase (SDHB, SDHC, SDHD and SDH5), and isocitrate dehydrogenase-1 and -2 (IDH1, IDH2)..
  3. Genetic Determinants of Uterine Fibroids in African-American and Caucasian Women
    Brahim Aissani; Fiscal Year: 2013
    ..1q43 encoding the tricaboxylic acid cycle (Krebs cycle) fumarate hydratase (FH) enzyme...
  4. Finding Genes for Uterine Fibroids
    Cynthia Morton; Fiscal Year: 2007
    ..and papillary renal cell carcinoma, resulted in the surprising finding of mutations in the gene for fumarate hydratase. Despite these important findings, we remain ignorant of the genes that predispose millions of women to ..
  5. Using Synthetic Lethality to Select Cancer Drug Targets
    William Kaelin; Fiscal Year: 2005
    ..Moreover, they may establish a new paradigm for the selection of anticancer drug targets based on inactivating mutations of TSG. ..
  6. A Luciferase Fusion Protein Library to Identify & Monitor Ubiquitylation Targets
    William Kaelin; Fiscal Year: 2008
    ..Reisolation of HIF in aims 2 and 3 would constitute proof of concept with respect to the potential utility of this approach. ..
  7. Real-Time Imaging of Hypoxia based on VHL Activity
    William Kaelin; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  8. 2006 Cancer Model Mechanisms
    William Kaelin; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  9. Genetic basis of myopathy with Paget disease of bone
    Virginia Kimonis; Fiscal Year: 2008
    ..e. effect on ATPase activity, protein-protein interactions, and hexamer formation). Study the VCP specific pathways in C2C12 cell lines (stably transfected wt and R155H VCP) during differentiation and under stress conditions...
  10. GENE CAUSING PAGET & LIMB-GIRDLE MUSCULAR DYSTROPHY
    Virginia Kimonis; Fiscal Year: 2003
    ..Delineation of the genetic component responsible for the LGMD/PDB phenotype should promise similar insight and facilitate in the design of novel treatment protocols for the two disorders. ..
  11. Characterization of Familial Myopathy & Paget Disease
    Virginia Kimonis; Fiscal Year: 2005
    ..Elucidation of the genetic defect will help us understand the pathogenesis of this multifaceted disorder and hopefully result in specific therapy. ..
  12. How Substrates Activate Fumarase and Glyoxalase Evolved
    Irwin Rose; Fiscal Year: 2005
    ..Since methylglyoxal is toxic to cells and must be removed by an active glyoxalse system, inhibition of a MSH based system could result in a treatment for many mycobacterial-based diseases such as tuberculosis. ..
  13. Characterization of Hemolysin A from Proteus mirabilis
    Todd Weaver; Fiscal Year: 2004
    ..The results may provide information regarding the hemolysin virulence factor within Proteus mirabilis and allow new drug design strategies for the treatment of Proteus-based urinary tract infections. ..
  14. Two-step therapeutic screen for mitochondrial epilepsies
    Manisha Patel; Fiscal Year: 2007
    ..This screening procedure will allow us to participate the the NINDS cooperative program designed to specifically develop candidate therapies for clinical development. [unreadable] [unreadable] [unreadable]..