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PMID: 10769039 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Plakoglobin suppresses epithelial proliferation and hair growth in vivo.

The Journal of cell biology ·Vol. 149 ·No. 2 ·2000-04-17 ·Pages 503-20

Charpentier E, Lavker RM, Acquista E, Cowin P

Abstract

Plakoglobin regulates cell adhesion by providing a modulatable connection between both classical and desmosomal cadherins and their respective cytoskeletal linker proteins. Both plakoglobin and the related protein beta-catenin are posttranscriptionally upregulated in response to Wnt-1 in cultured cells. Upregulation of beta-catenin has been implicated in potentiating hyperproliferation and tumor formation. To investigate the role of plakoglobin in these functions we expressed a full-length (PG) and an NH(2)-terminally truncated form of plakoglobin (DeltaN80PG) in mouse epidermis and hair follicles, tissues which undergo continuous and easily observed postnatal renewal and remodeling. Expression of these constructs results in stunted hair growth, a phenotype that has also been observed in transgenic mice expressing Wnt3 and Dvl2 (Millar et al. 1999). Hair follicles from PG and DeltaN80PG mice show premature termination of the growth phase (anagen) of the hair cycle, an event that is regulated in part by FGF5 (Hebert et al. 1994). The proliferative rate of the epidermal cells was reduced and apoptotic changes, which are associated with entry into the regressive phase of the hair follicle cycle (catagen), occurred earlier than usual.

MeSH Terms
Aging Animals Base Sequence Cell Adhesion Molecules/genetics,physiology Cell Division/physiology Cell Line, Transformed Cytoskeletal Proteins/genetics,physiology Desmoplakins Desmosomes/physiology,ultrastructure Epidermal Cells Epidermis/ultrastructure Epithelial Cells/cytology,ultrastructure Hair Follicle/cytology,growth & development,ultrastructure Humans Mice Mice, Transgenic Molecular Sequence Data Oligodeoxyribonucleotides Polymerase Chain Reaction Recombinant Proteins/metabolism Sequence Deletion Transfection gamma Catenin
Chemicals
Cell Adhesion Molecules Cytoskeletal Proteins Desmoplakins Oligodeoxyribonucleotides Recombinant Proteins gamma Catenin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Charpentier E
Departments of Cell Biology and Dermatology, New York University Medical School, New York 10016, USA.
Lavker R M
Acquista E
Cowin P
References (90)
90 references, click to expand
  1. beta-catenin is a target for the ubiquitin-proteasome pathway.
    EMBO J. 1997 Jul 1;16(13):3797-804 PMID: 9233789
  2. Serine phosphorylation-regulated ubiquitination and degradation of beta-catenin.
    J Biol Chem. 1997 Oct 3;272(40):24735-8 PMID: 9312064
  3. Analysis of the signaling activities of localization mutants of beta-catenin during axis specification in Xenopus.
    J Cell Biol. 1997 Oct 6;139(1):229-43 PMID: 9314542
  4. Roles of plakoglobin end domains in desmosome assembly.
    J Cell Sci. 1997 Oct;110 ( Pt 19):2359-71 PMID: 9410875
  5. Propagation and localization of Wnt signaling.
    Curr Opin Genet Dev. 1998 Aug;8(4):430-5 PMID: 9729719
  6. Strategies of epithelial repair: modulation of stem cell and transit amplifying cell proliferation.
    J Cell Sci. 1998 Oct;111 ( Pt 19):2867-75 PMID: 9730979
  7. Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling.
    Nature. 1998 Oct 1;395(6701):521-5 PMID: 9774110
  8. Drosophila Tcf and Groucho interact to repress Wingless signalling activity.
    Nature. 1998 Oct 8;395(6702):604-8 PMID: 9783586
  9. The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors.
    Nature. 1998 Oct 8;395(6702):608-12 PMID: 9783587
  10. Differential molecular interactions of beta-catenin and plakoglobin in adhesion, signaling and cancer.
    Curr Opin Cell Biol. 1998 Oct;10(5):629-39 PMID: 9818174
  11. De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin.
    Cell. 1998 Nov 25;95(5):605-14 PMID: 9845363
  12. Pontin52, an interaction partner of beta-catenin, binds to the TATA box binding protein.
    Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14787-92 PMID: 9843967
  13. WNT signaling in the control of hair growth and structure.
    Dev Biol. 1999 Mar 1;207(1):133-49 PMID: 10049570
  14. Modulation of cell proliferation by cytokeratins K10 and K16.
    Mol Cell Biol. 1999 Apr;19(4):3086-94 PMID: 10082575
  15. A common human skin tumour is caused by activating mutations in beta-catenin.
    Nat Genet. 1999 Apr;21(4):410-3 PMID: 10192393
  16. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells.
    Nature. 1999 Apr 1;398(6726):422-6 PMID: 10201372
  17. Highly persistent label-retaining cells in the hair follicles of mice and their fate following induction of anagen.
    J Invest Dermatol. 1999 Apr;112(4):470-5 PMID: 10201531
  18. Activation of the protein kinase Akt/PKB by the formation of E-cadherin-mediated cell-cell junctions. Evidence for the association of phosphatidylinositol 3-kinase with the E-cadherin adhesion complex.
    J Biol Chem. 1999 Jul 2;274(27):19347-51 PMID: 10383446
  19. Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis.
    Cell. 1999 Jul 23;98(2):147-57 PMID: 10428027
  20. Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene.
    EMBO J. 1999 Nov 1;18(21):5931-42 PMID: 10545105
  21. The novel tyrosine kinase ZAK1 activates GSK3 to direct cell fate specification.
    Cell. 1999 Nov 12;99(4):399-408 PMID: 10571182
  22. The keratinocyte growth-differentiation switch.
    Front Biosci. 1998 May 15;3:d502-8 PMID: 9600879
  23. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  24. Calcium regulation of growth and differentiation of mouse epidermal cells in culture.
    Cell. 1980 Jan;19(1):245-54 PMID: 6153576
  25. Calcium regulation of cell-cell contact and differentiation of epidermal cells in culture. An ultrastructural study.
    Exp Cell Res. 1983 Jan;143(1):127-42 PMID: 6186504
  26. The complement of desmosomal plaque proteins in different cell types.
    J Cell Biol. 1985 Oct;101(4):1442-54 PMID: 2413044
  27. The amino-terminal domain of desmoplakin binds to plakoglobin and clusters desmosomal cadherin-plakoglobin complexes.
    J Cell Biol. 1997 Nov 3;139(3):773-84 PMID: 9348293
  28. Regulation of beta-catenin levels and localization by overexpression of plakoglobin and inhibition of the ubiquitin-proteasome system.
    J Cell Biol. 1997 Dec 1;139(5):1325-35 PMID: 9382877
  29. Analysis of apoptosis during hair follicle regression (catagen)
    Am J Pathol. 1997 Dec;151(6):1601-17 PMID: 9403711
  30. Novel regulatory interactions revealed by studies of murine limb pattern in Wnt-7a and En-1 mutants.
    Development. 1997 Dec;124(24):5021-32 PMID: 9362463
  31. Wnt signaling: why is everything so negative?
    Curr Opin Cell Biol. 1998 Apr;10(2):182-7 PMID: 9561842
  32. Effects of forced expression of an NH2-terminal truncated beta-Catenin on mouse intestinal epithelial homeostasis.
    J Cell Biol. 1998 May 4;141(3):765-77 PMID: 9566975
  33. Defining the interactions between intermediate filaments and desmosomes.
    J Cell Biol. 1998 Jun 1;141(5):1229-41 PMID: 9606214
  34. Regulation of armadillo by a Drosophila APC inhibits neuronal apoptosis during retinal development.
    Cell. 1998 Jun 26;93(7):1171-82 PMID: 9657150
  35. E-Cadherin-dependent growth suppression is mediated by the cyclin-dependent kinase inhibitor p27(KIP1).
    J Cell Biol. 1998 Jul 27;142(2):557-71 PMID: 9679152
  36. Directed expression of keratin 16 to the progenitor basal cells of transgenic mouse skin delays skin maturation.
    J Cell Biol. 1998 Aug 24;142(4):1035-51 PMID: 9722615
  37. Identification of c-MYC as a target of the APC pathway.
    Science. 1998 Sep 4;281(5382):1509-12 PMID: 9727977
  38. Plakoglobin: a protein common to different kinds of intercellular adhering junctions.
    Cell. 1986 Sep 26;46(7):1063-73 PMID: 3530498
  39. Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line.
    J Cell Biol. 1988 Mar;106(3):761-71 PMID: 2450098
  40. Tissue-specific and differentiation-specific expression of a human K14 keratin gene in transgenic mice.
    Proc Natl Acad Sci U S A. 1989 Mar;86(5):1563-7 PMID: 2466292
  41. Molecular cloning and amino acid sequence of human plakoglobin, the common junctional plaque protein.
    Proc Natl Acad Sci U S A. 1989 Jun;86(11):4027-31 PMID: 2726765
  42. Ectopic expression of the proto-oncogene int-1 in Xenopus embryos leads to duplication of the embryonic axis.
    Cell. 1989 Sep 22;58(6):1075-84 PMID: 2673541
  43. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis.
    Cell. 1990 Jun 29;61(7):1329-37 PMID: 2364430
  44. Hair follicular stem cells: the bulge-activation hypothesis.
    J Invest Dermatol. 1991 May;96(5):77S-78S PMID: 2022884
  45. Transgenic mice provide new insights into the role of TGF-alpha during epidermal development and differentiation.
    Genes Dev. 1991 May;5(5):714-27 PMID: 1709129
  46. Morphoregulatory activities of NCAM and N-cadherin can be accounted for by G protein-dependent activation of L- and N-type neuronal Ca2+ channels.
    Cell. 1991 Oct 4;67(1):21-33 PMID: 1680564
  47. A role for the E-cadherin cell-cell adhesion molecule during tumor progression of mouse epidermal carcinogenesis.
    J Cell Biol. 1991 Oct;115(2):517-33 PMID: 1918152
  48. Interleukin 6: insights to its function in skin by overexpression in transgenic mice.
    Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5068-72 PMID: 1375756
  49. In vivo expression and stoichiometric sulfation of the artificial protein sulfophilin, a polymer of tyrosine sulfation sites.
    J Biol Chem. 1992 Aug 5;267(22):15938-42 PMID: 1639821
  50. Targeting expression of keratinocyte growth factor to keratinocytes elicits striking changes in epithelial differentiation in transgenic mice.
    EMBO J. 1993 Mar;12(3):973-86 PMID: 7681397
  51. Induction of a secondary body axis in Xenopus by antibodies to beta-catenin.
    J Cell Biol. 1993 Oct;123(2):477-84 PMID: 8408227
  52. Expression of Wnt-1 in PC12 cells results in modulation of plakoglobin and E-cadherin and increased cellular adhesion.
    J Cell Biol. 1993 Dec;123(6 Pt 2):1857-65 PMID: 8276903
  53. Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin.
    J Cell Biol. 1994 Mar;124(5):729-41 PMID: 8120095
  54. Cells within the bulge region of mouse hair follicle transiently proliferate during early anagen: heterogeneity and functional differences of various hair cycles.
    Differentiation. 1994 Jan;55(2):127-36 PMID: 8143930
  55. Alterations in beta-catenin phosphorylation and plakoglobin expression in human breast cancer cells.
    Cancer Res. 1994 Jul 1;54(13):3544-52 PMID: 8012979
  56. Differential transformation of mammary epithelial cells by Wnt genes.
    Mol Cell Biol. 1994 Sep;14(9):6278-86 PMID: 8065359
  57. FGF5 as a regulator of the hair growth cycle: evidence from targeted and spontaneous mutations.
    Cell. 1994 Sep 23;78(6):1017-25 PMID: 7923352
  58. Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice.
    Genes Dev. 1994 Nov 15;8(22):2691-703 PMID: 7958926
  59. Beta-catenin mediates the interaction of the cadherin-catenin complex with epidermal growth factor receptor.
    J Cell Biol. 1994 Dec;127(5):1375-80 PMID: 7962096
  60. Embryonic axis induction by the armadillo repeat domain of beta-catenin: evidence for intracellular signaling.
    J Cell Biol. 1995 Mar;128(5):959-68 PMID: 7876319
  61. Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein.
    Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):3046-50 PMID: 7708772
  62. Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate.
    Genes Dev. 1995 Mar 15;9(6):700-13 PMID: 7537238
  63. Identification of distinct classes and functional domains of Wnts through expression of wild-type and chimeric proteins in Xenopus embryos.
    Mol Cell Biol. 1995 May;15(5):2625-34 PMID: 7739543
  64. Anterior axis duplication in Xenopus induced by the over-expression of the cadherin-binding protein plakoglobin.
    Proc Natl Acad Sci U S A. 1995 May 9;92(10):4522-6 PMID: 7753837
  65. The human plakoglobin gene localizes on chromosome 17q21 and is subjected to loss of heterozygosity in breast and ovarian cancers.
    Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6384-8 PMID: 7604000
  66. Structural basis for DNA bending by the architectural transcription factor LEF-1.
    Nature. 1995 Aug 31;376(6543):791-5 PMID: 7651541
  67. Isolation and utilization of epidermal keratinocytes for oncogene research.
    Methods Enzymol. 1995;254:3-20 PMID: 8531694
  68. Hedgehog and Bmp genes are coexpressed at many diverse sites of cell-cell interaction in the mouse embryo.
    Dev Biol. 1995 Nov;172(1):126-38 PMID: 7589793
  69. Expression of a dominant negative mutant of epidermal growth factor receptor in the epidermis of transgenic mice elicits striking alterations in hair follicle development and skin structure.
    EMBO J. 1995 Nov 1;14(21):5216-23 PMID: 7489711
  70. Lack of beta-catenin affects mouse development at gastrulation.
    Development. 1995 Nov;121(11):3529-37 PMID: 8582267
  71. Suppression of tumorigenicity by plakoglobin: an augmenting effect of N-cadherin.
    J Cell Biol. 1996 Apr;133(1):199-209 PMID: 8601608
  72. Forced expression of E-cadherin in the mouse intestinal epithelium slows cell migration and provides evidence for nonautonomous regulation of cell fate in a self-renewing system.
    Genes Dev. 1996 Apr 15;10(8):985-96 PMID: 8608945
  73. Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly.
    Science. 1996 May 17;272(5264):1023-6 PMID: 8638126
  74. Desmosomal cadherin binding domains of plakoglobin.
    J Biol Chem. 1996 May 3;271(18):10904-9 PMID: 8631907
  75. A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled.
    J Biol Chem. 1996 Feb 23;271(8):4468-76 PMID: 8626800
  76. Lef1 expression is activated by BMP-4 and regulates inductive tissue interactions in tooth and hair development.
    Genes Dev. 1996 Jun 1;10(11):1382-94 PMID: 8647435
  77. The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3.
    Genes Dev. 1996 Jun 15;10(12):1443-54 PMID: 8666229
  78. Functional interaction of beta-catenin with the transcription factor LEF-1.
    Nature. 1996 Aug 15;382(6592):638-42 PMID: 8757136
  79. XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos.
    Cell. 1996 Aug 9;86(3):391-9 PMID: 8756721
  80. A new member of the frizzled family from Drosophila functions as a Wingless receptor.
    Nature. 1996 Jul 18;382(6588):225-30 PMID: 8717036
  81. Cytoskeleton-membrane interactions.
    Curr Opin Cell Biol. 1996 Feb;8(1):56-65 PMID: 8791403
  82. Murine Wnt10a and Wnt10b: cloning and expression in developing limbs, face and skin of embryos and in adults.
    Oncogene. 1996 Oct 3;13(7):1537-44 PMID: 8875992
  83. Signal transduction through beta-catenin and specification of cell fate during embryogenesis.
    Genes Dev. 1996 Oct 15;10(20):2527-39 PMID: 8895655
  84. CAM-FGF receptor interactions: a model for axonal growth.
    Mol Cell Neurosci. 1996;8(2-3):99-111 PMID: 8918827
  85. Embryonic heart and skin defects in mice lacking plakoglobin.
    Dev Biol. 1996 Dec 15;180(2):780-5 PMID: 8954745
  86. A member of the Frizzled protein family mediating axis induction by Wnt-5A.
    Science. 1997 Mar 14;275(5306):1652-4 PMID: 9054360
  87. Stabilization of beta-catenin by genetic defects in melanoma cell lines.
    Science. 1997 Mar 21;275(5307):1790-2 PMID: 9065403
  88. Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF.
    Cell. 1997 Mar 21;88(6):789-99 PMID: 9118222
  89. Cytoplasmically anchored plakoglobin induces a WNT-like phenotype in Xenopus.
    Dev Biol. 1997 May 1;185(1):67-81 PMID: 9169051
  90. The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.
    Cell. 1997 Jul 11;90(1):181-92 PMID: 9230313
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
Published
2000-04-17
Pages
503-20
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2175163
Subset
IM
Grants
NIGMS NIH HHS · GM47429 · United States
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