S Constantinescu

Summary

Affiliation: Ludwig Institute for Cancer Research
Country: Belgium

Publications

  1. ncbi request reprint Stemness, fusion and renewal of hematopoietic and embryonic stem cells
    S Constantinescu
    Signal Transduction Unit, Ludwig Institute for Cancer Research, Christian de Duve Institute of Cellular Pathology, UCL, Avenue Hippocrate 74, UCL 74 4, Brussels B 1200, Belgium
    J Cell Mol Med 7:103-12. 2003
  2. doi request reprint Mining for JAK-STAT mutations in cancer
    Stefan N Constantinescu
    Ludwig Institute for Cancer Research and de Duve Institute, Universite Catholique de Louvain, Brussels B 1200, Belgium
    Trends Biochem Sci 33:122-31. 2008
  3. pmc Extracellular domain N-glycosylation controls human thrombopoietin receptor cell surface levels
    Roxana I Albu
    Ludwig Institute for Cancer Research Brussels, Belgium
    Front Endocrinol (Lausanne) 2:71. 2011
  4. pmc JAK2 V617F constitutive activation requires JH2 residue F595: a pseudokinase domain target for specific inhibitors
    Alexandra Dusa
    Ludwig Institute for Cancer Research Ltd, Brussels, Belgium
    PLoS ONE 5:e11157. 2010
  5. doi request reprint Activating Janus kinase pseudokinase domain mutations in myeloproliferative and other blood cancers
    Stefan N Constantinescu
    Ludwig Institute for Cancer Research and Université Catholique de Louvain, de Duve Institute, Brussels B1200, Belgium
    Biochem Soc Trans 41:1048-54. 2013
  6. doi request reprint Small-molecule inhibitors in myeloproliferative neoplasms: are we aiming for the right targets?
    Stefan N Constantinescu
    Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium
    Hematology Am Soc Hematol Educ Program 2012:553-60. 2012
  7. pmc NetPath: a public resource of curated signal transduction pathways
    Kumaran Kandasamy
    Institute of Bioinformatics, International Tech Park, Bangalore 560066, India
    Genome Biol 11:R3. 2010
  8. ncbi request reprint The erythropoietin receptor transmembrane domain mediates complex formation with viral anemic and polycythemic gp55 proteins
    Stefan N Constantinescu
    Ludwig Institute for Cancer Research and University of Louvain, Brussels B 1200, Belgium
    J Biol Chem 278:43755-63. 2003
  9. ncbi request reprint Structural requirements of the extracellular to transmembrane domain junction for erythropoietin receptor function
    Katharina F Kubatzky
    Ludwig Institute for Cancer Research, Bruxelles 1200, Belgium
    J Biol Chem 280:14844-54. 2005
  10. ncbi request reprint Active and inactive orientations of the transmembrane and cytosolic domains of the erythropoietin receptor dimer
    Nadine Seubert
    Ludwig Institute for Cancer Research, Brussels B 1200, Belgium
    Mol Cell 12:1239-50. 2003

Collaborators

Detail Information

Publications30

  1. ncbi request reprint Stemness, fusion and renewal of hematopoietic and embryonic stem cells
    S Constantinescu
    Signal Transduction Unit, Ludwig Institute for Cancer Research, Christian de Duve Institute of Cellular Pathology, UCL, Avenue Hippocrate 74, UCL 74 4, Brussels B 1200, Belgium
    J Cell Mol Med 7:103-12. 2003
    ..The homeodomain protein Nanog has been shown to be crucial for the embryonic stem cell renewal and pluripotency. However, the cardinal question of how stemness is preserved in the early embryo and adult stem cells remains opened...
  2. doi request reprint Mining for JAK-STAT mutations in cancer
    Stefan N Constantinescu
    Ludwig Institute for Cancer Research and de Duve Institute, Universite Catholique de Louvain, Brussels B 1200, Belgium
    Trends Biochem Sci 33:122-31. 2008
    ..Recent discoveries also suggest that mutated JAK proteins will be potent targets for anti-cancer therapy...
  3. pmc Extracellular domain N-glycosylation controls human thrombopoietin receptor cell surface levels
    Roxana I Albu
    Ludwig Institute for Cancer Research Brussels, Belgium
    Front Endocrinol (Lausanne) 2:71. 2011
    ..We discuss how mutations around TpoR N-glycosylation sites might contribute to inefficient receptor traffic and disease...
  4. pmc JAK2 V617F constitutive activation requires JH2 residue F595: a pseudokinase domain target for specific inhibitors
    Alexandra Dusa
    Ludwig Institute for Cancer Research Ltd, Brussels, Belgium
    PLoS ONE 5:e11157. 2010
    ....
  5. doi request reprint Activating Janus kinase pseudokinase domain mutations in myeloproliferative and other blood cancers
    Stefan N Constantinescu
    Ludwig Institute for Cancer Research and Université Catholique de Louvain, de Duve Institute, Brussels B1200, Belgium
    Biochem Soc Trans 41:1048-54. 2013
    ..More structural information of the full-length JAK coupled to cytokine receptors might be required in order to define the structural basis of JH1 activation by JH2 mutants and eventually obtain mutant-specific inhibitors. ..
  6. doi request reprint Small-molecule inhibitors in myeloproliferative neoplasms: are we aiming for the right targets?
    Stefan N Constantinescu
    Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium
    Hematology Am Soc Hematol Educ Program 2012:553-60. 2012
    ....
  7. pmc NetPath: a public resource of curated signal transduction pathways
    Kumaran Kandasamy
    Institute of Bioinformatics, International Tech Park, Bangalore 560066, India
    Genome Biol 11:R3. 2010
    ..We anticipate NetPath to become a consolidated resource for human signaling pathways that should enable systems biology approaches...
  8. ncbi request reprint The erythropoietin receptor transmembrane domain mediates complex formation with viral anemic and polycythemic gp55 proteins
    Stefan N Constantinescu
    Ludwig Institute for Cancer Research and University of Louvain, Brussels B 1200, Belgium
    J Biol Chem 278:43755-63. 2003
    ..As unliganded EpoR forms TM-dependent but inactive homodimers, we propose that the EpoR can be activated to different extents by homodimeric gp55 proteins, depending on the conformation of the gp55 protein dimer in the TM region...
  9. ncbi request reprint Structural requirements of the extracellular to transmembrane domain junction for erythropoietin receptor function
    Katharina F Kubatzky
    Ludwig Institute for Cancer Research, Bruxelles 1200, Belgium
    J Biol Chem 280:14844-54. 2005
    ..This structure is important for EpoR function because replacement of this motif by consecutive leucines rendered the receptor constitutively active...
  10. ncbi request reprint Active and inactive orientations of the transmembrane and cytosolic domains of the erythropoietin receptor dimer
    Nadine Seubert
    Ludwig Institute for Cancer Research, Brussels B 1200, Belgium
    Mol Cell 12:1239-50. 2003
    ..The active and inactive conformations were independently identified by computational searches for low-energy TM dimeric structures. We propose a specific EpoR-activated interface and suggest its use for structural and signaling studies...
  11. pmc Amyloidogenic processing but not amyloid precursor protein (APP) intracellular C-terminal domain production requires a precisely oriented APP dimer assembled by transmembrane GXXXG motifs
    Pascal Kienlen-Campard
    Center for Neurosciences, Experimental Pharmacology Unit, Universite Catholique de Louvain, B 1200 Brussels, Belgium
    J Biol Chem 283:7733-44. 2008
    ..Increased dimerization of the TM APP C-terminal domain did not affect AICD production...
  12. ncbi request reprint High-throughput gateway bicistronic retroviral vectors for stable expression in mammalian cells: exploring the biologic effects of STAT5 overexpression
    Yohan Royer
    Ludwig Institute for Cancer Research, Brussels, Belgium
    DNA Cell Biol 23:355-65. 2004
    ..We discuss possible applications of the new vectors for cell signaling and expression cloning...
  13. ncbi request reprint Differential STAT5 signaling by ligand-dependent and constitutively active cytokine receptors
    Virginie Moucadel
    Ludwig Institute for Cancer Research, Brussels B 1200, Belgium
    J Biol Chem 280:13364-73. 2005
    ....
  14. pmc Acute lymphoblastic leukemia-associated JAK1 mutants activate the Janus kinase/STAT pathway via interleukin-9 receptor alpha homodimers
    Tekla Hornakova
    Ludwig Institute for Cancer Research, Brussels Branch and de Duve Institute, Universite Catholique de Louvain, B 1200 Brussels, Belgium
    J Biol Chem 284:6773-81. 2009
    ..Similar results were observed with IL-2Rbeta. Taken together, our results show that IL-9Ralpha and IL-2Rbeta homodimers efficiently mediate constitutive activation of ALL-associated JAK1 mutants...
  15. pmc An amphipathic motif at the transmembrane-cytoplasmic junction prevents autonomous activation of the thrombopoietin receptor
    Judith Staerk
    Ludwig Institute for Cancer Research, Universite Catholique de Louvain, Avenue Hippocrate 74, UCL 75 4, 1200 Brussels, Belgium
    Blood 107:1864-71. 2006
    ..These residues may be targets for activating mutations in humans. Such a motif may exist in other receptors to prevent ligand-independent activation and to allow signaling via multiple flexible interfaces...
  16. pmc What is the role of amyloid precursor protein dimerization?
    Naouel Ben Khalifa
    Universite Catholique de Louvain, Institute of Neuroscience, Brussels, Belgium
    Cell Adh Migr 4:268-72. 2010
    ..observations raise important questions about APP processing and function: How and where is APP dimerizing? What is the role of dimerization in APP processing and function? Can dimerization be targeted by small molecule therapeutics?..
  17. ncbi request reprint Janus kinases affect thrombopoietin receptor cell surface localization and stability
    Yohan Royer
    Ludwig Institute for Cancer Research, Brussels B 1200, Belgium
    J Biol Chem 280:27251-61. 2005
    ..We discuss the relevance of our results to the reported defects of TpoR processing in myeloproliferative diseases and to the mechanisms of Tpo signaling and clearance via the TpoR...
  18. doi request reprint Induction of myeloproliferative disorder and myelofibrosis by thrombopoietin receptor W515 mutants is mediated by cytosolic tyrosine 112 of the receptor
    Christian Pecquet
    Ludwig Institute for Cancer Research, Brussels, Belgium
    Blood 115:1037-48. 2010
    ..We propose that TpoR cytosolic phosphorylated Y112 and flanking sequences could become targets for pharmacologic inhibition in MPNs...
  19. ncbi request reprint Role of tyrosine kinases and phosphatases in polycythemia vera
    Zhizhuang Joe Zhao
    Hematology Oncology Division, Department of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, 2220 Pierce Avenue, Nashville, TN 37232, USA
    Semin Hematol 42:221-9. 2005
    ..Other events may include defects in PTPs, but these remain to be characterized. Recent studies represent a great step forward in the molecular pathogenesis in PV and the development of targeted new drugs to treat the disease...
  20. pmc Helix packing and orientation in the transmembrane dimer of gp55-P of the spleen focus forming virus
    Wei Liu
    Department of Biochemistry and Cell Biology, Stony Brook University, New York 11794, USA
    Biophys J 89:1194-202. 2005
    ..We discuss the implications of the structure of the gp55-P transmembrane dimer for activation of the Epo receptor...
  21. pmc The Jak2V617F oncogene associated with myeloproliferative diseases requires a functional FERM domain for transformation and for expression of the Myc and Pim proto-oncogenes
    Gerlinde Wernig
    Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Blood 111:3751-9. 2008
    ..Overall, our results suggest that constitutive activation of Jak2 requires an intact FERM domain for a transforming phenotype, and is necessary for activation of the major target of Jak2, STAT5...
  22. pmc Development of human protein reference database as an initial platform for approaching systems biology in humans
    Suraj Peri
    McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA
    Genome Res 13:2363-71. 2003
    ..hprd.org to the academic community. This unified bioinformatics platform will be useful in cataloging and mining the large number of proteomic interactions and alterations that will be discovered in the postgenomic era...
  23. doi request reprint The JAK2V617F mutation can occur in a hematopoietic stem cell that exhibits no proliferative advantage: a case of human allogeneic transplantation
    Kristien Van Pelt
    Blood 112:921-2. 2008
  24. doi request reprint The Stat3-activating Tyk2 V678F mutant does not up-regulate signaling through the type I interferon receptor but confers ligand hypersensitivity to a homodimeric receptor
    Milica Gakovic
    Cytokine Signaling Unit, CNRS URA 1961, Institut Pasteur, Paris 75724, France
    J Biol Chem 283:18522-9. 2008
    ..Thus, despite the catalytic gain of function of Tyk2 V678F, the effect on ligand-induced signaling is manifest only when two mutant enzymes are juxtaposed via the homodimeric receptor...
  25. ncbi request reprint A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera
    Chloe James
    INSERM U362, Institut Gustave Roussy, Paris XI University, PR1, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France
    Nature 434:1144-8. 2005
    ..As this mutation is also found in other myeloproliferative disorders, this unique mutation will permit a new molecular classification of these disorders and novel therapeutical approaches...
  26. ncbi request reprint The ubiquitin-mediated degradation of Jak1 modulates osteoclastogenesis by limiting interferon-beta-induced inhibitory signaling
    Youngkyun Lee
    Department of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Korea
    Blood 111:885-93. 2008
    ..These data suggest that the regulation of Jak1 expression during osteoclast differentiation might serve as an intrinsic mechanism that determines osteoclast lineage commitment by modulating the negative regulation by IFN-beta...
  27. ncbi request reprint A JAK2 mutation in myeloproliferative disorders: pathogenesis and therapeutic and scientific prospects
    Chloe James
    INSERM U362, Institut Gustave Roussy, Paris XI University, PR1, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France
    Trends Mol Med 11:546-54. 2005
    ..Such a recurrent and unique mutation leading to a tyrosine kinase deregulation would make a suitable target for the development of specific therapies...
  28. ncbi request reprint JAK1 and Tyk2 activation by the homologous polycythemia vera JAK2 V617F mutation: cross-talk with IGF1 receptor
    Judith Staerk
    Ludwig Institute for Cancer Research, Brussels B 1200, Belgium
    J Biol Chem 280:41893-9. 2005
    ..We suggest that mutations in the JAK1 and Tyk2 genes may be identified as initial molecular defects in human cancers and autoimmune diseases...
  29. ncbi request reprint Microarray analysis of LIF/Stat3 transcriptional targets in embryonic stem cells
    Dalila Sekkai
    INSERM U362, Institut Gustave Roussy, 94805 Villejuif Cedex, France
    Stem Cells 23:1634-42. 2005
    ..Furthermore, chromatin immunoprecipitation experiment demonstrated that Stat3 is recruited to the promoter of aes1 in ES cells. These data demonstrated that the aes1 gene is a direct transcriptional target of Stat3 in ES cells...
  30. pmc Inhibitors of amyloid toxicity based on beta-sheet packing of Abeta40 and Abeta42
    Takeshi Sato
    Department of Biochemistry and Cell Biology, Center for Structural Biology, Stony Brook University, Stony Brook, New York 11794 5215, USA
    Biochemistry 45:5503-16. 2006
    ..Importantly, the designed peptide inhibitors significantly reduce the toxicity induced by Abeta42 on cultured rat cortical neurons...