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PMID: 8917536 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Inhibition of granulocytic differentiation by mNotch1.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 23 ·1996-11-12 ·Pages 13014-9

Milner LA, Bigas A, Kopan R, Brashem-Stein C, Bernstein ID, Martin DI

Abstract

Effective hematopoiesis requires the commitment of pluripotent and multipotent stem cells to distinct differentiation pathways, proliferation and maturation of cells in the various lineages, and preservation of pluripotent progenitors to provide continuous renewal of mature blood cells. While the importance of positive and negative cytokines in regulating proliferation and maturation of hematopoietic cells has been well documented, the factors and molecular processes involved in lineage commitment and self-renewal of multipotent progenitors have not yet been defined. In other developmental systems, cellular interactions mediated by members of the Notch gene family have been shown to influence cell fate determination by multipotent progenitors. We previously described the expression of the human Notch1 homolog, TAN-1, in immature hematopoietic precursors. We now demonstrate that constitutive expression of the activated intracellular domain of mouse Notch1 in 32D myeloid progenitors inhibits granulocytic differentiation and permits expansion of undifferentiated cells, findings consistent with the known function of Notch in other systems.

MeSH Terms
Amino Acid Sequence Animals Cell Differentiation Cell Division Granulocytes/cytology,physiology Hematopoietic Stem Cells/cytology,physiology Humans Kinetics Membrane Proteins/biosynthesis,physiology Mice Molecular Sequence Data Morphogenesis Polymerase Chain Reaction Protein Sorting Signals/chemistry Receptor, Notch1 Receptor, Notch2 Receptors, Cell Surface/biosynthesis,physiology Recombinant Proteins/biosynthesis Retroviridae Transcription Factors Transfection
Chemicals
Membrane Proteins NOTCH1 protein, human NOTCH2 protein, human Notch1 protein, mouse Notch2 protein, mouse Protein Sorting Signals Receptor, Notch1 Receptor, Notch2 Receptors, Cell Surface Recombinant Proteins Transcription Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Milner L A
Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle 98104, USA.
Bigas A
Kopan R
Brashem-Stein C
Bernstein I D
Martin D I
References (50)
50 references, click to expand
  1. Nucleotide sequence from the neurogenic locus notch implies a gene product that shares homology with proteins containing EGF-like repeats.
    Cell. 1985 Dec;43(3 Pt 2):567-81 PMID: 3935325
  2. The transcriptional control of hematopoiesis.
    Blood. 1996 May 15;87(10):4025-39 PMID: 8639758
  3. Cytokine-dependent granulocytic differentiation. Regulation of proliferative and differentiative responses in a murine progenitor cell line.
    J Immunol. 1987 Jun 1;138(11):3829-35 PMID: 2438328
  4. glp-1 and lin-12, genes implicated in distinct cell-cell interactions in C. elegans, encode similar transmembrane proteins.
    Cell. 1989 Aug 11;58(3):553-63 PMID: 2758466
  5. Improved retroviral vectors for gene transfer and expression.
    Biotechniques. 1989 Oct;7(9):980-2, 984-6, 989-90 PMID: 2631796
  6. Xotch, the Xenopus homolog of Drosophila notch.
    Science. 1990 Sep 21;249(4975):1438-41 PMID: 2402639
  7. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms.
    Cell. 1991 Aug 23;66(4):649-61 PMID: 1831692
  8. A homolog of Drosophila Notch expressed during mammalian development.
    Development. 1991 Sep;113(1):199-205 PMID: 1764995
  9. Making a difference: the role of cell-cell interactions in establishing separate identities for equivalent cells.
    Cell. 1992 Jan 24;68(2):271-81 PMID: 1365402
  10. Expression of an activated Notch-related int-3 transgene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands.
    Genes Dev. 1992 Mar;6(3):345-55 PMID: 1372276
  11. Mouse mammary tumor gene int-3: a member of the notch gene family transforms mammary epithelial cells.
    J Virol. 1992 Apr;66(4):2594-9 PMID: 1312643
  12. Inhibition of myeloid differentiation by the helix-loop-helix protein Id.
    Science. 1992 Mar 27;255(5052):1700-2 PMID: 1372755
  13. Choosing a cell fate: a view from the Notch locus.
    Trends Genet. 1991 Nov-Dec;7(11-12):403-8 PMID: 1668193
  14. Expression pattern of Motch, a mouse homolog of Drosophila Notch, suggests an important role in early postimplantation mouse development.
    Development. 1992 Jul;115(3):737-44 PMID: 1425352
  15. Motch A and motch B--two mouse Notch homologues coexpressed in a wide variety of tissues.
    Exp Cell Res. 1993 Feb;204(2):364-72 PMID: 8440332
  16. Notch2: a second mammalian Notch gene.
    Development. 1992 Dec;116(4):931-41 PMID: 1295745
  17. Mouse notch: expression in hair follicles correlates with cell fate determination.
    J Cell Biol. 1993 May;121(3):631-41 PMID: 8486742
  18. Human homologs of a Drosophila Enhancer of split gene product define a novel family of nuclear proteins.
    Nat Genet. 1992 Oct;2(2):119-27 PMID: 1303260
  19. Differentiation and proliferation of hematopoietic stem cells.
    Blood. 1993 Jun 1;81(11):2844-53 PMID: 8499622
  20. Expression of an extracellular deletion of Xotch diverts cell fate in Xenopus embryos.
    Cell. 1993 May 21;73(4):659-71 PMID: 8500162
  21. Specific truncations of Drosophila Notch define dominant activated and dominant negative forms of the receptor.
    Cell. 1993 Jul 30;74(2):319-29 PMID: 8343959
  22. Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo.
    Cell. 1993 Jul 30;74(2):331-45 PMID: 8343960
  23. Control of cell fate in C. elegans by a GLP-1 peptide consisting primarily of ankyrin repeats.
    Nature. 1993 Aug 12;364(6438):632-5 PMID: 8350921
  24. Antineurogenic phenotypes induced by truncated Notch proteins indicate a role in signal transduction and may point to a novel function for Notch in nuclei.
    Genes Dev. 1993 Oct;7(10):1949-65 PMID: 8406001
  25. An activated Notch receptor blocks cell-fate commitment in the developing Drosophila eye.
    Nature. 1993 Oct 7;365(6446):555-7 PMID: 8413612
  26. Hematopoietic regulators: redundancy or subtlety?
    Blood. 1993 Dec 15;82(12):3515-23 PMID: 8260692
  27. Notch: neurogenesis is only part of the picture.
    Cell. 1993 Dec 31;75(7):1245-7 PMID: 8269507
  28. A human homologue of the Drosophila developmental gene, Notch, is expressed in CD34+ hematopoietic precursors.
    Blood. 1994 Apr 15;83(8):2057-62 PMID: 7512837
  29. The role of the enhancer of split complex during cell fate determination in Drosophila.
    Dev Suppl. 1993;:139-48 PMID: 8049468
  30. The novel Notch homologue mouse Notch 3 lacks specific epidermal growth factor-repeats and is expressed in proliferating neuroepithelium.
    Mech Dev. 1994 May;46(2):123-36 PMID: 7918097
  31. The suppressor of hairless protein participates in notch receptor signaling.
    Cell. 1994 Oct 21;79(2):273-82 PMID: 7954795
  32. The intracellular domain of mouse Notch: a constitutively activated repressor of myogenesis directed at the basic helix-loop-helix region of MyoD.
    Development. 1994 Sep;120(9):2385-96 PMID: 7956819
  33. T cell leukemia-associated human Notch/translocation-associated Notch homologue has I kappa B-like activity and physically interacts with nuclear factor-kappa B proteins in T cells.
    J Exp Med. 1996 May 1;183(5):2025-32 PMID: 8642313
  34. Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles.
    J Exp Med. 1996 May 1;183(5):2283-91 PMID: 8642337
  35. Notch4/int-3, a mammary proto-oncogene, is an endothelial cell-specific mammalian Notch gene.
    Development. 1996 Jul;122(7):2251-9 PMID: 8681805
  36. Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J kappa/Su(H).
    Curr Biol. 1995 Dec 1;5(12):1416-23 PMID: 8749394
  37. An activated Notch suppresses neurogenesis and myogenesis but not gliogenesis in mammalian cells.
    Development. 1994 Sep;120(9):2421-30 PMID: 7956822
  38. Delta-notch signaling and Drosophila cell fate choice.
    Dev Biol. 1994 Dec;166(2):415-30 PMID: 7813766
  39. Three genes in the human MHC class III region near the junction with the class II: gene for receptor of advanced glycosylation end products, PBX2 homeobox gene and a notch homolog, human counterpart of mouse mammary tumor gene int-3.
    Genomics. 1994 Sep 15;23(2):408-19 PMID: 7835890
  40. The human NOTCH1, 2, and 3 genes are located at chromosome positions 9q34, 1p13-p11, and 19p13.2-p13.1 in regions of neoplasia-associated translocation.
    Genomics. 1994 Nov 15;24(2):253-8 PMID: 7698746
  41. Notch signaling.
    Science. 1995 Apr 14;268(5208):225-32 PMID: 7716513
  42. Developmental genetics. The Notch connection.
    Nature. 1995 Jun 29;375(6534):736-7 PMID: 7596404
  43. Signalling downstream of activated mammalian Notch.
    Nature. 1995 Sep 28;377(6547):355-8 PMID: 7566092
  44. The neurogenic suppressor of hairless DNA-binding protein mediates the transcriptional activation of the enhancer of split complex genes triggered by Notch signaling.
    Genes Dev. 1995 Nov 1;9(21):2598-608 PMID: 7590238
  45. Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity.
    Genes Dev. 1995 Nov 1;9(21):2609-22 PMID: 7590239
  46. Developmental signaling. Vertebrate ligands for Notch.
    Curr Biol. 1995 Sep 1;5(9):966-9 PMID: 8542284
  47. Truncated mammalian Notch1 activates CBF1/RBPJk-repressed genes by a mechanism resembling that of Epstein-Barr virus EBNA2.
    Mol Cell Biol. 1996 Mar;16(3):952-9 PMID: 8622698
  48. Hematopoiesis: how does it happen?
    Curr Opin Cell Biol. 1995 Dec;7(6):870-7 PMID: 8608018
  49. Signal transduction by activated mNotch: importance of proteolytic processing and its regulation by the extracellular domain.
    Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1683-8 PMID: 8643690
  50. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product.
    Mol Cell Biol. 1985 Dec;5(12):3610-6 PMID: 3915782
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.23.13014
Published
1996-11-12
Pages
13014-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC24038
Subset
IM
Grants
NHLBI NIH HHS · 5RO1HC 48790 · United States
NICHD NIH HHS · P30 HD28834 · United States
Databases
GENBANK
U31881
External Links
PubMed source DOI: 10.1073/pnas.93.23.13014 PMC Full Text View journal details
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