Article thumbnail

Components of the nuclear signaling cascade that regulate collagenase gene expression in response to integrin-derived signals

By 

Abstract

We have shown previously that the expression of collagenase is upregulated in rabbit synovial fibroblasts cultured on a substrate of antibody to the alpha 5 chain of the alpha 5 beta 1 integrin fibronectin receptor or on the 120-kD cell-binding chymotryptic fragment of plasma fibronectin, but remains at basal levels in cells plated on intact plasma fibronectin. We now have identified some of the components of a signaling pathway that couples the fibronectin receptor to the induction of collagenase transcription. We studied the control of collagenase gene expression in cells adhering to the 120-kD fragment of fibronectin, to antifibronectin receptor antibody, or to plasma fibronectin by transiently introducing promoter-reporter constructs into rabbit synovial fibroblasts before plating cells on these matrices. The constructs contained segments of the human collagenase promoter regulating transcription of chloramphenicol acyl transferase. Expression of constructs containing the -1200/-42-bp segment or the - 139/-42-bp segment of the collagenase promoter inserted upstream from the reporter gene was induced to similar extents in cells plated on the 120-kD fragment of fibronectin or on anti-fibronectin receptor antibody, relative to that in fibroblasts plated on fibronectin. The expression of the construct containing the -66/-42-bp segment of the promoter was not regulated and was similar to that of the parent pBLCAT2 plasmid, suggesting that the -139/-67 region of the collagenase promoter, which contains PEA3- and AP1-binding sites, regulates the transcription of collagenase caused by integrin-derived signals. Expression of a reporter construct containing only the PEA3 and AP1 sites in the collagenase promoter (-90/-67) also increased in cells plated on the 120-kD fragment of fibronectin or on anti-fibronectin receptor antibody, relative to that in cells plated on fibronectin. Mutations in either the AP1 or PEA3 site of this minimal promoter abrogated its activity in cells plated on these inductive ligands. Expression of c-fos mRNA increased within 1 h of plating cells on the 120-kD fibronectin fragment or on anti-fibronectin receptor antibody, relative to that in cells plated on fibronectin. c-Fos protein accumulated in the nuclei of fibroblasts within 10 min of plating on the 120-kD fibronectin fragment. The increase in c-Fos was required for the increase in collagenase in cells plated on the 120-kD fibronectin fragment: incubation of cells with antisense, but not sense, c-fos oligonucleotides diminished both basal and induced expression of the - 139/-42 collagenase promoter-reporter construct and decreased expression of the endogenous collagenase gene.(ABSTRACT TRUNCATED AT 400 WORDS

Topics: Articles
Publisher: The Rockefeller University Press
OAI identifier: oai:pubmedcentral.nih.gov:2291183
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles

Citations

  1. (1987). 12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5'-flanking region.
  2. (1987). A gene for rabbit synovial cell collagenase: member of a family of metalloproteinases that degrade the connective tissue matrix.
  3. (1993). A link between cyclin A expression and adhesion-dependent cell cycle progression.
  4. (1986). A nonchromatographic assay for expression of the chloramphenicol acetyl transferase gene in eucaryotic cells.
  5. (1993). A polyomavirus enhancer A-binding protein-3 site and Ets-2 protein have a major role in the 12-O-tetradecanoylphorbol-13 acetate response of the human stromelysin gene.
  6. (1989). Activation of HIV gene expression during monocyte differentiation by induction of NF-KB.
  7. (1991). Activation of human CD4 T lymphocytes: interaction of fibronectin with VLA-5 receptor on CD4 cells induces the AP-1 transcription factor.
  8. (1991). Activation of protein kinase C decreases phosphorylation of c-Jun at sites that negatively regulate its DNA-binding activity.
  9. (1990). Adherence-dependent increase in human monocyte PDGF(B) mRNA is associated with increases in c-los, c-]un, and EGR2 mRNA.
  10. (1993). Adhesion to fibronectin stimulates inositol lipid synthesis and enhances PDGF-induced inositol lipid breakdown.
  11. (1989). Antibodies: A Laboratory Manual.
  12. (1988). Cell adhesion induces expression of growth-associated genes in suspension-arrested fibroblasts.
  13. (1993). Co-purification of mitogen-activated protein kinases with phorbol ester-induced c-Jun kinase activity in U937 leukaemic ceils.
  14. (1984). Collagenase is a major gene product of induced rabbit synovial fibroblasts.
  15. (1986). Commitment to expression of the metalloendopeptidases, collagenase and stromelysin: relationship of inducing events to changes in eytoskeletal architecture.
  16. (1991). Complete structure of the human gene for 92-kDa type IV collagenase. Divergent regulation of expression for the 92- and 72-kilodalton enzyme genes in HT-1080 ceils.
  17. (1990). Control of intracellular pH and growth by fibronectin in capillary endothelial cells.
  18. (1991). Control of mammary epithelial differentiation: basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity.
  19. (1990). Disruption of cytoskeletal structures results in the induction of the urokinase-type plasminogen activator gene expression.
  20. (1991). Disruption of the cytoskeleton with cytochalasin D induces c-los gene expression. Exp. Cell Res.
  21. (1990). Epidermal growth factor stimulation of stromelysin mRNA in rat fibroblasts requires induction of proto-oncogenes e-los and c-jun and activation of protein kinase
  22. (1991). Essential AP-1 and PEA3 binding elements in the human urokinase enhancer display cell type-specific activity.
  23. (1992). Evidence that Ha-Ras mediates two distinguishable intraeellular signals activated by v-Src.
  24. (1989). Expression of raf oncogenes activates the PEA1 transcription factor motif.
  25. (1990). Extracellular matrix and hormones transcriptionally regulate bovine 13-casein 5' sequences in stably transfected mouse mammary ceils.
  26. (1989). Fibronectin inhibits the terminal differentiation of human keratinocytes.
  27. (1991). Fos is phosphorylated by p34cdc2, cAMP-dependent protein kinase and protein kinase C at multiple sites clustered within regulatory regions.
  28. (1988). Growth factors regulate transin gene expression by c-los-dependent and c-los-independent pathways. Science (Wash.
  29. (1986). Human los gene. Cold Spring Harbor Syrup.
  30. (1992). Identification and characterization of Ref-1, a nuclear protein that facilitates AP-1 DNA-binding activity.
  31. (1991). Identification of a serum- and phorbol ester-responsive element in the murine tissue inhibitor of metaUoproteinase gene.
  32. (1992). Integrin-dependent phosphorylation and activation of the protein tyrosine kinase pp125FAK in platelets.
  33. (1992). Integrins: versatility, modulation, and signaling in cell adhesion.
  34. (1994). Interleukin I alpha mediates collagenase synthesis stimulated by phorbol 12-myristate 13-acetate.
  35. (1991). Interleukin-1 or phorbol induction of the stromelysin promoter requires an element that cooperates with AP-1. Nucleic Acids Res.
  36. (1990). Interleukin-1 stimulates and all-trans-retinoic acid inhibits collagenase gene expression through its 5' activator-protein-i-binding site.
  37. (1719). lntegrin-induced Nuclear Signaling
  38. (1987). Modification of fos proteins: phosphorylation of c-fos, but not v-fos, is stimulated by 12-tetradecanoyl-phorbol-13-acetate and serum.
  39. (1989). Molecular biology of collagen degradation.
  40. (1989). Molecular Cloning: A Laboratory Manual. 2nd Edition.
  41. (1991). Multiple integrins share the ability to induce elevation of intracellular pH.
  42. (1993). Novel phorbol ester response region in the collagenase promoter binds Fos
  43. (1991). Nuclear targets for transcriptional regulation by oncogenes. Trends Genet.
  44. (1987). Occupation of the extracellular matrix receptor, integrin, is a control point for myogenic differentiation.
  45. (1992). Oncoprotein-mediated signalling cascade stimulates c-Jun activity by phosphorylation of serines 63 and 73.
  46. (1991). PEA1 and PEA3 enhancer elements are primary components of the polyomavirus late transcription initiator element.
  47. (1987). Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans.acting factor.
  48. (1990). Phosphorylation of the C terminus of Fos protein is required for transcriptional transrepression of the c-fos promoter.
  49. (1992). Primary structure and function of stromelysin/transin in cartilage matrix turnover. Matrix Suppl.
  50. (1989). Prolonged activation of jun and collagenase genes by tumour necrosis factor-a.
  51. (1993). Protein kinase Ca activates RAF-1 by direct phosphorylation.
  52. (1982). Recombinant genomes which express chloramphenieol acetyltransferase in mammalian cells.
  53. (1990). Redox regulation of Fos and Jun DNA-binding activity in vitro.
  54. (1990). Regulation of collagenase gene expression by okadaic acid, an inhibitor of protein phosphatases. Cell Regul.
  55. (1993). Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells.
  56. (1993). Role of cytokines and inflammatory mediators in tissue destruction.
  57. (1991). Role of Raf-1 serine/threonine protein kinase in growth factor signal transduction.
  58. (1992). Signal transduction by integrin receptors for extracellular matrix: cooperative processing of extracellular information.
  59. (1993). Signal transduction from the extracellular matrix.
  60. (1989). Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression.
  61. (1993). SPARC, a secreted protein associated with morphogenesis and tissue remodeling, induces expression of metalloproteinases in fibroblasts through a novel extracellular matrix-dependent pathway.
  62. (1992). Specific members of the Jun protein family regulate coilagenase expression in response to various extracellular stimuli.
  63. (1991). Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes los and jun.
  64. (1990). TGF-IM inhibition of transin/stromelysin gene expression is mediated through a Fos binding sequence.
  65. (1991). The AP-1 sequence is necessary but not sufficient for phorbol induction of collagenase in fibroblasts.
  66. (1991). The AP-1 site is required for basal expression but is not necessary for TPA-response of the human stromelysin gene. Nucleic Acids Res.
  67. (1991). The c-Ets oncoprotein activates the stromelysin promoter through the same elements as several non-nuclear oncoproteins.
  68. (1990). The collagenase gene promoter contains a TPA and oncogene-responsive unit encompassing the PEA3 and AP-1 binding sites.
  69. (1994). The extracellular matrix hgands fibronectin and tenascin collaborate in regulating collagenase gene expression in fibroblasts.
  70. (1988). Trans-acting protein factors and the regulation of eurkaryotic transcription: lessons from studies on DNA tumor viruses. Genes Dev.
  71. (1990). Transcription factor interactions: selectors of positive or negative regulation from a single DNA element. Science (Wash.
  72. (1990). Transcriptional activation and repression by Fos are independent functions: the C terminus represses immediate-early gene expression via CArG elements.
  73. (1988). Transcriptional activation by the SV40 AP-1 recognition element in yeast is mediated by a factor similar to AP-1 that is distinct from GCN4.
  74. (1989). Transcriptional regulation of human stromelysin.
  75. (1993). UV-induced activation of AP-1 involves obligatory extranuclear steps including Raf-1 kinase.
  76. (1988). v-jun encodes a nuclear protein with enhancer binding properties of AP-1.
  77. (1985). Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res.
  78. (1989). Yeast YAP1 encodes a novel form of the jun family of transcriptional activator proteins. Genes Dev.