Raphael Kopan

Summary

Affiliation: Washington University School of Medicine
Country: USA

Publications

  1. ncbi request reprint Aph-2/Nicastrin: an essential component of gamma-secretase and regulator of Notch signaling and Presenilin localization
    Raphael Kopan
    Department of Pharmacology and Molecular Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    Neuron 33:321-4. 2002
  2. pmc The extracellular domain of Notch2 increases its cell-surface abundance and ligand responsiveness during kidney development
    Zhenyi Liu
    Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Dev Cell 25:585-98. 2013
  3. pmc The contribution of Notch1 to nephron segmentation in the developing kidney is revealed in a sensitized Notch2 background and can be augmented by reducing Mint dosage
    Kameswaran Surendran
    Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Dev Biol 337:386-95. 2010
  4. ncbi request reprint Analysis of Notch function in presomitic mesoderm suggests a gamma-secretase-independent role for presenilins in somite differentiation
    Stacey S Huppert
    Department of Molecular Biology and Pharmacology, Division of Dermatology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Dev Cell 8:677-88. 2005
  5. ncbi request reprint gamma-secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning or initial morphogenesis
    Yonghua Pan
    Department of Molecular Biology and Pharmacology, Division of Dermatology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Dev Cell 7:731-43. 2004
  6. pmc Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP, a sentinel for epidermal integrity
    Shadmehr Demehri
    Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri, United States of America
    PLoS Biol 6:e123. 2008
  7. pmc Canonical Notch signaling in the developing lung is required for determination of arterial smooth muscle cells and selection of Clara versus ciliated cell fate
    Mitsuru Morimoto
    Department of Developmental Biology and Division of Dermatology, Washington University School of Medicine, Box 8103, Saint Louis, MO 63110 1095, USA
    J Cell Sci 123:213-24. 2010
  8. pmc The absence of a microbiota enhances TSLP expression in mice with defective skin barrier but does not affect the severity of their allergic inflammation
    Laura J Yockey
    Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri, USA
    J Invest Dermatol 133:2714-21. 2013
  9. ncbi request reprint Notch signaling is required for the formation of mesangial cells from a stromal mesenchyme precursor during kidney development
    Scott C Boyle
    Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    Development 141:346-54. 2014
  10. pmc Mapping the consequence of Notch1 proteolysis in vivo with NIP-CRE
    Marc Vooijs
    Department of Molecular Biology and Pharmacology and the Department of Medicine, Division of Dermatology, Washington University Medical School, St Louis, MO 63110, USA
    Development 134:535-44. 2007

Detail Information

Publications65

  1. ncbi request reprint Aph-2/Nicastrin: an essential component of gamma-secretase and regulator of Notch signaling and Presenilin localization
    Raphael Kopan
    Department of Pharmacology and Molecular Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    Neuron 33:321-4. 2002
    ..The transmembrane protein Nicastrin has been found to associate with Presenilin, Notch, and APP. Recent biochemical and genetic studies have focused on elucidating the function of this protein...
  2. pmc The extracellular domain of Notch2 increases its cell-surface abundance and ligand responsiveness during kidney development
    Zhenyi Liu
    Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Dev Cell 25:585-98. 2013
    ..This context-specific asymmetry in NICD release efficiency is further enhanced by Fringe. Our results indicate that an elevated N1 surface level could compensate for the loss of N2 signal in specific cell contexts. ..
  3. pmc The contribution of Notch1 to nephron segmentation in the developing kidney is revealed in a sensitized Notch2 background and can be augmented by reducing Mint dosage
    Kameswaran Surendran
    Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Dev Biol 337:386-95. 2010
    ....
  4. ncbi request reprint Analysis of Notch function in presomitic mesoderm suggests a gamma-secretase-independent role for presenilins in somite differentiation
    Stacey S Huppert
    Department of Molecular Biology and Pharmacology, Division of Dermatology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Dev Cell 8:677-88. 2005
    ..These data clarify multiple roles for Notch signaling during segmentation and suggest that the earliest stages of somitogenesis are regulated by both Notch-dependent and Notch-independent functions of presenilin...
  5. ncbi request reprint gamma-secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning or initial morphogenesis
    Yonghua Pan
    Department of Molecular Biology and Pharmacology, Division of Dermatology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Dev Cell 7:731-43. 2004
    ....
  6. pmc Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP, a sentinel for epidermal integrity
    Shadmehr Demehri
    Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri, United States of America
    PLoS Biol 6:e123. 2008
    ..These observations demonstrate that local skin perturbations can drive a lethal systemic disease and have important implications for a wide range of humoral and autoimmune diseases with skin manifestations...
  7. pmc Canonical Notch signaling in the developing lung is required for determination of arterial smooth muscle cells and selection of Clara versus ciliated cell fate
    Mitsuru Morimoto
    Department of Developmental Biology and Division of Dermatology, Washington University School of Medicine, Box 8103, Saint Louis, MO 63110 1095, USA
    J Cell Sci 123:213-24. 2010
    ..These analyses suggest that the impact of gamma-secretase inhibitors on branching in vitro reflect a non-cell autonomous contribution from endothelial or vSMC-derived signals...
  8. pmc The absence of a microbiota enhances TSLP expression in mice with defective skin barrier but does not affect the severity of their allergic inflammation
    Laura J Yockey
    Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri, USA
    J Invest Dermatol 133:2714-21. 2013
    ..These findings suggest a role for the microbiota in ameliorating stress signals released by keratinocytes in response to perturbation in cutaneous barrier function. ..
  9. ncbi request reprint Notch signaling is required for the formation of mesangial cells from a stromal mesenchyme precursor during kidney development
    Scott C Boyle
    Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    Development 141:346-54. 2014
    ..Together, these data demonstrate a unique origin of mesangial cells and demonstrate a novel, redundant function for Notch receptors in mesangial cell specification, proliferation or survival during kidney development. ..
  10. pmc Mapping the consequence of Notch1 proteolysis in vivo with NIP-CRE
    Marc Vooijs
    Department of Molecular Biology and Pharmacology and the Department of Medicine, Division of Dermatology, Washington University Medical School, St Louis, MO 63110, USA
    Development 134:535-44. 2007
    ..These findings highlight an underappreciated layer of complexity of Notch signaling in vivo. Moreover, NIP-CRE represents a general strategy applicable for monitoring proteolysis-dependent signaling in vivo...
  11. ncbi request reprint Target selectivity of vertebrate notch proteins. Collaboration between discrete domains and CSL-binding site architecture determines activation probability
    Chin Tong Ong
    Department of Molecular Biology and Pharmacology, Division of Dermatology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 281:5106-19. 2006
    ....
  12. pmc Physiological notch signaling maintains bone homeostasis via RBPjk and Hey upstream of NFATc1
    Xiaolin Tu
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri, United States of America
    PLoS Genet 8:e1002577. 2012
    ..Thus, Notch-RBPjk signaling functions in part through Hey1-mediated inhibition of NFATc1 to suppress osteoblastogenesis, contributing to bone homeostasis in vivo...
  13. pmc Notch pathway activation can replace the requirement for Wnt4 and Wnt9b in mesenchymal-to-epithelial transition of nephron stem cells
    Scott C Boyle
    Departments of Developmental Biology and Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Development 138:4245-54. 2011
    ..After MET, Notch provides an instructive signal directing cells towards the proximal tubule lineage at the expense of other renal epithelial fates...
  14. pmc Epidermal Notch1 loss promotes skin tumorigenesis by impacting the stromal microenvironment
    Shadmehr Demehri
    Department of Developmental Biology, Division of Dermatology, Washington University School of Medicine, Saint Louis, MO 63110 1095, USA
    Cancer Cell 16:55-66. 2009
    ....
  15. pmc Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation
    Matthew J Hilton
    Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
    Nat Med 14:306-14. 2008
    ..Thus, mesenchymal progenitors may be expanded in vitro by activating the Notch pathway, whereas bone formation in vivo may be enhanced by transiently suppressing this pathway...
  16. pmc Rapid identification of homologous recombinants and determination of gene copy number with reference/query pyrosequencing (RQPS)
    Zhenyi Liu
    Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Genome Res 19:2081-9. 2009
    ..In addition, we also present a simple pyrosequencing-based protocol that could be used for the enrichment of homologous recombinant embryonic stem (ES) cells...
  17. pmc FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man
    Hila Barak
    Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8103, St Louis, MO 63110, USA
    Dev Cell 22:1191-207. 2012
    ..These findings identify a long-sought-after critical component of the nephron stem cell niche and hold promise for long-term culture and utilization of these progenitors in vitro...
  18. ncbi request reprint Ectodomain shedding and intramembrane cleavage of mammalian Notch proteins is not regulated through oligomerization
    Marc Vooijs
    Department of Molecular Biology and Pharmacology, Division of Dermatology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 279:50864-73. 2004
    ..Our results indicate that ligand-induced reversal of controlled TMD dimerization by the Notch extracellular domain is unlikely to underlie the regulatory mechanism of intramembranous cleavage...
  19. pmc Notch signaling in bulge stem cells is not required for selection of hair follicle fate
    Shadmehr Demehri
    Department of Developmental Biology, Division of Dermatology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Development 136:891-6. 2009
    ..Taken together, our findings yield detailed insight into the function of Notch signaling in hair follicle stem cells and reveal the mechanism of the replacement of Notch-deficient adult hair follicles by epidermal cysts...
  20. pmc Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin
    Shadmehr Demehri
    Department of Developmental Biology and Division of Dermatology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St Louis, MO 63110 1095, USA
    Cancer Cell 22:494-505. 2012
    ..Importantly, TSLP overexpression in wild-type skin also caused resistance to tumorigenesis, confirming that TSLP functions as a tumor suppressor in the skin...
  21. pmc Gamma-secretase composed of PS1/Pen2/Aph1a can cleave notch and amyloid precursor protein in the absence of nicastrin
    Guojun Zhao
    Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 30:1648-56. 2010
    ..This PS1/Pen2/Aph1a complex, however, is highly unstable. Thus, NCT acts to stabilize gamma-secretase but is not required for substrate recognition...
  22. ncbi request reprint Notch1 and 2 cooperate in limb ectoderm to receive an early Jagged2 signal regulating interdigital apoptosis
    Yonghua Pan
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Box 8103, 660 S Euclid Avenue, St Louis, MO 63110, USA
    Dev Biol 286:472-82. 2005
    ..Thus, Notch signaling plays a non-autonomous role in digit septation...
  23. pmc Reduced Notch signaling leads to renal cysts and papillary microadenomas
    Kameswaran Surendran
    Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Am Soc Nephrol 21:819-32. 2010
    ....
  24. pmc Genetic interplays between Msx2 and Foxn1 are required for Notch1 expression and hair shaft differentiation
    Jing Cai
    Division of Dermatology, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Dev Biol 326:420-30. 2009
    ..Our results position Msx2 and Foxn1 upstream of Notch1 within the hair matrix and demonstrate that together these factors play a pivotal role in IRS, cortex and medulla differentiation...
  25. pmc Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron
    Hui Teng Cheng
    Department of Molecular Biology and Pharmacology at Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8103, St Louis, MO 63110, USA
    Development 134:801-11. 2007
    ..These results establish distinct (non-redundant), instructive roles for Notch receptors in nephron segmentation...
  26. pmc Molecular insights into segmentation along the proximal-distal axis of the nephron
    Raphael Kopan
    Department of Molecular Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Am Soc Nephrol 18:2014-20. 2007
    ..The underlying principles of regional cell signaling and transcriptional control organizing early segmentation are the subject of this review...
  27. pmc Presenilins, Notch dose control the fate of pancreatic endocrine progenitors during a narrow developmental window
    Corentin Cras-Méneur
    Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Genes Dev 23:2088-101. 2009
    ....
  28. ncbi request reprint Notch pathway is dispensable for adipocyte specification
    Amy M Nichols
    Department of Molecular Biology and Pharmacology and the Department of Medicine Division of Dermatology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Genesis 40:40-4. 2004
    ..We conclude that the "canonical" Notch signaling pathway is dispensable for adipocyte specification and differentiation from either mesenchymal or epithelial progenitors...
  29. pmc Chromatin-based mechanisms of renal epithelial differentiation
    Kameswaran Surendran
    Department of Developmental Biology, Washington University School of Medicine, 660 S Euclid Avenue, St Louis, MO 63110, USA
    J Am Soc Nephrol 22:1208-12. 2011
    ..Here we highlight some common mechanisms of cell differentiation and epigenetic regulation to discuss their implications for renal epithelial development, repair, and disease...
  30. ncbi request reprint NOTCH1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cells
    Shuting Bai
    Departments of Pathology and Immunology, Molecular Biology and Pharmacology, and Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    J Biol Chem 283:6509-18. 2008
    ..These observations raise caution that therapeutic inhibition of NOTCH signaling may adversely accelerate bone loss in humans...
  31. pmc Real-time imaging of notch activation with a luciferase complementation-based reporter
    Ma Xenia G Ilagan
    Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    Sci Signal 4:rs7. 2011
    ..These experiments showed that Notch-LCI is an effective approach for characterizing modulators that target Notch signaling and for studying pathway dynamics in normal and disease contexts...
  32. ncbi request reprint A requirement for Notch1 distinguishes 2 phases of definitive hematopoiesis during development
    Brandon K Hadland
    Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis MO 63110, USA
    Blood 104:3097-105. 2004
    ..Thus, Notch1 is required, in a cell-autonomous manner, for the establishment of long-term, definitive hematopoietic stem cells (HSCs)...
  33. pmc The crystal structure of a partial mouse Notch-1 ankyrin domain: repeats 4 through 7 preserve an ankyrin fold
    Olga Y Lubman
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Protein Sci 14:1274-81. 2005
    ..The structural preservation and stability of the C-terminal repeats shed a new light onto the mechanism of hetero-oligomeric assembly during Notch-mediated transcriptional activation...
  34. ncbi request reprint Analysis of transmembrane domain mutants is consistent with sequential cleavage of Notch by gamma-secretase
    Dilip Chandu
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurochem 96:228-35. 2006
    ..Notch (and perhaps all gamma-secretase substrates) may be cleaved by sequential proteolysis starting at S3...
  35. pmc rtTA toxicity limits the usefulness of the SP-C-rtTA transgenic mouse
    Mitsuru Morimoto
    Department of Developmental Biology, Division of Dermatology, Washington University School of Medicine, Saint Louis, MO 63110, USA
    Dev Biol 325:171-8. 2009
    ..These studies demonstrate the importance of using appropriate SP-C-rtTA only controls in all experiments...
  36. ncbi request reprint Long-range, nonautonomous effects of activated Notch1 on tissue homeostasis in the nail
    Meei Hua Lin
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
    Dev Biol 263:343-59. 2003
    ..These data support the existence of a novel, cell-nonautonomous role for Notch in maintaining homeostasis of stratified squamous epithelia by indirectly promoting mitosis in basally located cells...
  37. pmc Loss of RBPj in postnatal excitatory neurons does not cause neurodegeneration or memory impairments in aged mice
    Chihiro Sato
    Department of Developmental Biology, Washington University School of Medicine, St Louis, MO, USA
    PLoS ONE 7:e48180. 2012
    ..We conclude that the loss of canonical Notch signaling through the four receptors is not responsible for age-dependent neurodegeneration or learning and memory deficits seen in γ-secretase deficient mice...
  38. doi request reprint Simple copy number determination with reference query pyrosequencing (RQPS)
    Zhenyi Liu
    Department of Developmental Biology, School of Medicine, Washington University, St Louis, Missouri 63110, USA
    Cold Spring Harb Protoc 2010:pdb.prot5491. 2010
    ....
  39. pmc Bi-compartmental communication contributes to the opposite proliferative behavior of Notch1-deficient hair follicle and epidermal keratinocytes
    Jonghyeob Lee
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, Saint Louis, MO 63110, USA
    Development 134:2795-806. 2007
    ..These results suggest that Notch1 participates in a bi-compartmental signaling network that controls homeostasis, follicular proliferation rates and melanocyte population within the skin...
  40. pmc A presenilin dimer at the core of the gamma-secretase enzyme: insights from parallel analysis of Notch 1 and APP proteolysis
    Eric H Schroeter
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 100:13075-80. 2003
    ..We propose that gamma-secretase contains a PS dimer in its catalytic core, that binding of substrate is at a site separate from the active site, and that substrate is cleaved at the interface of two PS molecules...
  41. pmc Notch1 loss of heterozygosity causes vascular tumors and lethal hemorrhage in mice
    Zhenyi Liu
    Department of Developmental Biology, Washington University in St Louis School of Medicine, St Louis, Missouri, USA
    J Clin Invest 121:800-8. 2011
    ..Our strategy also can be broadly applied to induce sporadic in vivo loss of heterozygosity of any conditional alleles in progenitors that experience Notch1 activation...
  42. ncbi request reprint Gamma-secretase activity is dispensable for mesenchyme-to-epithelium transition but required for podocyte and proximal tubule formation in developing mouse kidney
    Hui Teng Cheng
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Development 130:5031-42. 2003
    ..These observations suggest that gamma-secretase activity, probably through activation of Notch, is required for maintaining a competent progenitor pool as well as for determining the proximal tubule and podocyte fates...
  43. ncbi request reprint Genetic mosaic analysis indicates that the bulb region of coat hair follicles contains a resident population of several active multipotent epithelial lineage progenitors
    Raphael Kopan
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Dev Biol 242:44-57. 2002
    ..This latter feature resembles the behavior of hematopoietic stem cells after bone marrow transplantation, and raises the question of whether this property may be shared by stem cells in other self-renewing epithelia...
  44. pmc The canonical Notch signaling pathway: unfolding the activation mechanism
    Raphael Kopan
    Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    Cell 137:216-33. 2009
    ..In this Review, we highlight recent studies in Notch signaling that reveal new molecular details about the regulation of ligand-mediated receptor activation, receptor proteolysis, and target selection...
  45. pmc A faster migrating variant masquerades as NICD when performing in vitro gamma-secretase assays with bacterially expressed Notch substrates
    Preston C Keller
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8231, St Louis, Missouri 63110, USA
    Biochemistry 45:5351-8. 2006
    ....
  46. ncbi request reprint Gamma-secretase: proteasome of the membrane?
    Raphael Kopan
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Nat Rev Mol Cell Biol 5:499-504. 2004
  47. ncbi request reprint The role of Notch signaling in specification of podocyte and proximal tubules within the developing mouse kidney
    Hui Teng Cheng
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
    Kidney Int 68:1951-2. 2005
    ....
  48. ncbi request reprint Notch: a membrane-bound transcription factor
    Raphael Kopan
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Cell Sci 115:1095-7. 2002
  49. pmc Moonlighting activity of presenilin in plants is independent of gamma-secretase and evolutionarily conserved
    Abha Khandelwal
    Department of Biology, Washington University, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 104:13337-42. 2007
    ..Introduction of PpPS into PS-deficient mouse embryonic fibroblasts rescues normal growth rates, demonstrating that at least some metazoan functions of PS are evolutionarily conserved...
  50. pmc Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens
    Ansuman T Satpathy
    Department of Pathology and Immunology, School of Medicine, Washington University in St Louis, Missouri, USA
    Nat Immunol 14:937-48. 2013
    ..rodentium, but CD103(+) cDCs dependent on the transcription factor Batf3 were not. Our results demonstrate a nonredundant function for CD11b(+) cDCs in the response to pathogens in vivo. ..
  51. doi request reprint Selective blockade of transport via SERCA inhibition: the answer for oncogenic forms of Notch?
    Ma Xenia G Ilagan
    Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    Cancer Cell 23:267-9. 2013
    ..In this issue of Cancer Cell, Roti and colleagues demonstrate that inhibiting SERCA calcium pumps preferentially impairs the maturation of the most common class of oncogenic Notch1 mutants, thus uncovering a potential therapeutic avenue...
  52. pmc AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch
    Jacob S Lee
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA
    Nat Immunol 13:144-51. 2012
    ..Thus, AHR was essential for ILC22 cells and postnatal intestinal lymphoid tissues. Moreover, ILC22 subsets were heterogeneous in their requirement for Notch and their effect on the generation of intestinal lymphoid tissues...
  53. ncbi request reprint Notch activation induces apoptosis in neural progenitor cells through a p53-dependent pathway
    Xudong Yang
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Dev Biol 269:81-94. 2004
    ..Together, these complementary gain-of-function and loss-of-function studies reveal a previously unappreciated role of Notch signaling in the regulation of apoptotic cell death during early mammalian neural development...
  54. ncbi request reprint Notch and Presenilin: regulated intramembrane proteolysis links development and degeneration
    Dennis Selkoe
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
    Annu Rev Neurosci 26:565-97. 2003
    ..Elucidating the detailed mechanism of Presenilin processing of membrane proteins is important for understanding diverse signal transduction pathways and potentially for treating and preventing Alzheimer's disease...
  55. ncbi request reprint The Notch ligands DLL1 and JAG2 act synergistically to regulate hair cell development in the mammalian inner ear
    Amy E Kiernan
    The Jackson Laboratory, Bar Harbor, ME 04609, USA
    Development 132:4353-62. 2005
    ..Our results demonstrate that the Notch pathway plays a dual role in regulating cellular differentiation and patterning in the cochlea, acting both through lateral inhibition and the control of cellular proliferation...
  56. ncbi request reprint F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturation
    Qi Dong Hu
    Department of Clinical Research, Singapore General Hospital, 169608, Singapore, Singapore
    Cell 115:163-75. 2003
    ..Expression of constitutively active Notch1 or Notch2 does not upregulate MAG. Thus, F3/contactin specifically initiates a Notch/Deltex1 signaling pathway that promotes oligodendrocyte maturation and myelination...
  57. ncbi request reprint Intramembrane proteolysis: theme and variations
    Michael S Wolfe
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
    Science 305:1119-23. 2004
    ....
  58. pmc Notch and presenilin regulate cellular expansion and cytokine secretion but cannot instruct Th1/Th2 fate acquisition
    Chin Tong Ong
    Department of Developmental Biology, Washington University School of Medicine, Saint Louis, Missouri, United States of America
    PLoS ONE 3:e2823. 2008
    ..The controversies surrounding the role of Notch and presenilins in Th1/Th2 polarization may reflect their role as genetic modifiers of T-helper cells differentiation...
  59. ncbi request reprint A garden of Notch-ly delights
    Gerry Weinmaster
    Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1737, USA
    Development 133:3277-82. 2006
    ..Hosted by the Cantoblanco Workshops on Biology and organized by Tom Gridley, José Luis de la Pompa and Juan Carlos Izpisúa Belmonte, the meeting covered diverse aspects of this important signaling pathway...
  60. ncbi request reprint Three-dimensional structure of the gamma-secretase complex
    Toshihiko Ogura
    Neuroscience Research Institute and Biological Information Research Center BIRC, National Institute of Advanced Industrial Science and Technology AIST, Umezono 1 1 4, Tsukuba, Ibaraki 305 8568, Japan
    Biochem Biophys Res Commun 343:525-34. 2006
    ..Some of the dimples in the putative transmembrane region may house the catalytic site. The large dimensions are consistent with the observation that gamma-secretase activity resides within a high molecular weight complex...
  61. ncbi request reprint Notch1 signaling influences v2 interneuron and motor neuron development in the spinal cord
    Xudong Yang
    Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
    Dev Neurosci 28:102-17. 2006
    ..These results provide support for a role of Notch1 in neuronal subtype specification in the ventral spinal cord...
  62. ncbi request reprint Potential role of presenilin-regulated signaling pathways in sporadic neurodegeneration
    Edward H Koo
    Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA
    Nat Med 10:S26-33. 2004
    ..In this article, the possibility that these presenilin-regulated molecules may contribute to neurodegeneration is reviewed...
  63. ncbi request reprint Differentiation and gene regulation: toward a holistic understanding of animal development: intercellular communication and transcriptional regulation are two sides of the same coin
    Alan Michelson
    Curr Opin Genet Dev 12:499-502. 2002
  64. ncbi request reprint Anchoring notch genetics and biochemistry; structural analysis of the ankyrin domain sheds light on existing data
    Olga Y Lubman
    Department of Molecular Biology and Pharmacology and the Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63104 USA
    Mol Cell 13:619-26. 2004
    ....
  65. pmc Quantitative dissection of the Notch:CSL interaction: insights into the Notch-mediated transcriptional switch
    Olga Y Lubman
    T C Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, MD, USA
    J Mol Biol 365:577-89. 2007
    ..These results support an emerging molecular mechanism for the displacement of co-repressors from DNA-bound CSL by NICD...