Gene Symbol: Jup
Description: junction plakoglobin
Alias: Ctnng, D930025P04Rik, junction plakoglobin, desmoplakin III, desmoplakin-3, gamma-catenin
Species: mouse
Products:     Jup

Top Publications

  1. Nottebaum A, Cagna G, Winderlich M, Gamp A, Linnepe R, Polaschegg C, et al. VE-PTP maintains the endothelial barrier via plakoglobin and becomes dissociated from VE-cadherin by leukocytes and by VEGF. J Exp Med. 2008;205:2929-45 pubmed publisher
    ..In conclusion, leukocytes interacting with endothelial cells rapidly dissociate VE-PTP from VE-cadherin, weakening endothelial cell contacts via a mechanism that requires plakoglobin but not beta-catenin...
  2. Butz S, Stappert J, Weissig H, Kemler R. Plakoglobin and beta-catenin: distinct but closely related. Science. 1992;257:1142-4 pubmed
  3. Ozawa M, Ringwald M, Kemler R. Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule. Proc Natl Acad Sci U S A. 1990;87:4246-50 pubmed
    ..From these results we conclude that the cytoplasmic anchorage of uvomorulin is of major biological importance. ..
  4. Bierkamp C, Mclaughlin K, Schwarz H, Huber O, Kemler R. Embryonic heart and skin defects in mice lacking plakoglobin. Dev Biol. 1996;180:780-5 pubmed
    ..The skin phenotype in plakoglobin-deficient mice is reminiscent of the human blistering disease, epidermolytic hyperkeratosis. ..
  5. Huelsken J, Vogel R, Erdmann B, Cotsarelis G, Birchmeier W. beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell. 2001;105:533-45 pubmed
    ..Further analysis demonstrates that beta-catenin is essential for fate decisions of skin stem cells: in the absence of beta-catenin, stem cells fail to differentiate into follicular keratinocytes, but instead adopt an epidermal fate. ..
  6. Gallicano G, Kouklis P, Bauer C, Yin M, Vasioukhin V, Degenstein L, et al. Desmoplakin is required early in development for assembly of desmosomes and cytoskeletal linkage. J Cell Biol. 1998;143:2009-22 pubmed
  7. Yin T, Getsios S, Caldelari R, Kowalczyk A, Muller E, Jones J, et al. Plakoglobin suppresses keratinocyte motility through both cell-cell adhesion-dependent and -independent mechanisms. Proc Natl Acad Sci U S A. 2005;102:5420-5 pubmed
  8. Yin T, Getsios S, Caldelari R, Godsel L, Kowalczyk A, Muller E, et al. Mechanisms of plakoglobin-dependent adhesion: desmosome-specific functions in assembly and regulation by epidermal growth factor receptor. J Biol Chem. 2005;280:40355-63 pubmed
    ..As a target for modulation by EGF, regulation of PG-dependent adhesion may play an important role during wound healing and tumor metastasis. ..
  9. Ruiz P, Brinkmann V, Ledermann B, Behrend M, Grund C, Thalhammer C, et al. Targeted mutation of plakoglobin in mice reveals essential functions of desmosomes in the embryonic heart. J Cell Biol. 1996;135:215-25 pubmed

More Information


  1. Haegel H, Larue L, Ohsugi M, Fedorov L, Herrenknecht K, Kemler R. Lack of beta-catenin affects mouse development at gastrulation. Development. 1995;121:3529-37 pubmed
    ..Our results demonstrate that, although beta-catenin is expressed rather ubiquitously, it is specifically required in the ectodermal cell layer. ..
  2. Richardson R, Dixon J, Malhotra S, Hardman M, Knowles L, Boot Handford R, et al. Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch. Nat Genet. 2006;38:1329-34 pubmed
    ..Our results indicate that Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch and that Irf6 and Sfn interact genetically in this process. ..
  3. Dusek R, Godsel L, Chen F, Strohecker A, Getsios S, Harmon R, et al. Plakoglobin deficiency protects keratinocytes from apoptosis. J Invest Dermatol. 2007;127:792-801 pubmed
  4. Cowin P, Kapprell H, Franke W, Tamkun J, Hynes R. Plakoglobin: a protein common to different kinds of intercellular adhering junctions. Cell. 1986;46:1063-73 pubmed
    ..We discuss the significance of this protein, for which the name plakoglobin is proposed, in terms of its interaction with such biochemically diverse membrane domains and their different types of associated cytoskeletal filaments. ..
  5. Ozawa M, Baribault H, Kemler R. The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. EMBO J. 1989;8:1711-7 pubmed
    ..The characterization of these proteins provides a first molecular basis for a possible cytoplasmic anchorage of uvomorulin to the cytoskeleton. ..
  6. Franke W, Goldschmidt M, Zimbelmann R, Mueller H, Schiller D, Cowin P. Molecular cloning and amino acid sequence of human plakoglobin, the common junctional plaque protein. Proc Natl Acad Sci U S A. 1989;86:4027-31 pubmed
    ..7 kilobases) was detected in certain human tumor cell lines. This longer mRNA may be represented by a second type of plakoglobin cDNA, which contains an insertion of 297 nucleotides in the 3' non-coding region. ..
  7. Li J, Swope D, Raess N, Cheng L, Muller E, Radice G. Cardiac tissue-restricted deletion of plakoglobin results in progressive cardiomyopathy and activation of {beta}-catenin signaling. Mol Cell Biol. 2011;31:1134-44 pubmed publisher
    Mutations in the plakoglobin (JUP) gene have been identified in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients...
  8. Zhou J, Qu J, Yi X, Graber K, Huber L, Wang X, et al. Upregulation of gamma-catenin compensates for the loss of beta-catenin in adult cardiomyocytes. Am J Physiol Heart Circ Physiol. 2007;292:H270-6 pubmed
    ..The results suggest that upregulation of gamma-catenin can compensate for the loss of beta-catenin in cardiomyocytes to maintain normal cardiac structure and function. ..
  9. Williamson L, Raess N, Caldelari R, Zakher A, de Bruin A, Posthaus H, et al. Pemphigus vulgaris identifies plakoglobin as key suppressor of c-Myc in the skin. EMBO J. 2006;25:3298-309 pubmed
    ..Besides a completely novel insight into PV pathogenesis, these data identify PG as a potent modulator of epithelial homeostasis via its role as a key suppressor of c-Myc. ..
  10. Ihrie R, Marques M, Nguyen B, Horner J, Papazoglu C, Bronson R, et al. Perp is a p63-regulated gene essential for epithelial integrity. Cell. 2005;120:843-56 pubmed
    ..These findings demonstrate that Perp is a key effector in the p63 developmental program, playing an essential role in an adhesion subprogram central to epithelial integrity and homeostasis. ..
  11. Cheng X, Mihindukulasuriya K, Den Z, Kowalczyk A, Calkins C, Ishiko A, et al. Assessment of splice variant-specific functions of desmocollin 1 in the skin. Mol Cell Biol. 2004;24:154-63 pubmed
    ..However, a comparison of our mutants with dsc1-null mice suggests that the Dsc1 extracellular domain is necessary to maintain structural integrity of the skin. ..
  12. Li D, Zhang W, Liu Y, Haneline L, Shou W. Lack of plakoglobin in epidermis leads to keratoderma. J Biol Chem. 2012;287:10435-43 pubmed publisher
    Loss-of-function mutation of Jup has been associated with Naxos disease, which is characterized by arrhythmogenic cardiomyopathy and the cutaneous disorder palmoplantar keratoderma...
  13. Shimizu M, Fukunaga Y, Ikenouchi J, Nagafuchi A. Defining the roles of beta-catenin and plakoglobin in LEF/T-cell factor-dependent transcription using beta-catenin/plakoglobin-null F9 cells. Mol Cell Biol. 2008;28:825-35 pubmed
    ..We also clearly demonstrate that plakoglobin is insufficient for LEF/TCF-dependent transcriptional activation by Wnt-3a in F9 cells. ..
  14. Vasioukhin V, Bowers E, Bauer C, Degenstein L, Fuchs E. Desmoplakin is essential in epidermal sheet formation. Nat Cell Biol. 2001;3:1076-85 pubmed
    ..DP is therefore required for assembly of functional desmosomes, maintaining cytoskeletal architecture and reinforcing membrane attachments essential for stable intercellular adhesion. ..
  15. Huelsken J, Vogel R, Brinkmann V, Erdmann B, Birchmeier C, Birchmeier W. Requirement for beta-catenin in anterior-posterior axis formation in mice. J Cell Biol. 2000;148:567-78 pubmed
    ..Our data demonstrate that beta-catenin function is essential in anterior-posterior axis formation in the mouse, and experiments with chimeric embryos show that this function is required in the embryonic ectoderm. ..
  16. Aberle H, Bierkamp C, Torchard D, Serova O, Wagner T, Natt E, et al. 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;92:6384-8 pubmed
    ..Our results, together with the present knowledge about the biological function of plakoglobin, suggest that plakoglobin might represent a putative tumor suppressor gene for breast and ovarian cancers. ..
  17. Butz S, Kemler R. Distinct cadherin-catenin complexes in Ca(2+)-dependent cell-cell adhesion. FEBS Lett. 1994;355:195-200 pubmed
    ..A similar distinct association with catenins is also found for other cadherins. Comparison of different cell lines revealed that the relative amounts of the two complexes vary depending on cell types. ..
  18. Lin C, Fisher A, Yin Y, Maruyama T, Veith G, Dhandha M, et al. The inductive role of Wnt-?-Catenin signaling in the formation of oral apparatus. Dev Biol. 2011;356:40-50 pubmed publisher
    ..We provide genetic evidence that disruption of either signaling pathway results in severe microglossia. Altogether, we demonstrate a dynamic role for Wnt-?-Catenin signaling in the development of the oral apparatus...
  19. de Bruin A, Caldelari R, Williamson L, Suter M, Hunziker T, Wyder M, et al. Plakoglobin-dependent disruption of the desmosomal plaque in pemphigus vulgaris. Exp Dermatol. 2007;16:468-75 pubmed
    ..These results identify PG as a principle effector of the PVIgG-induced signals downstream of c-Myc that disrupt the desmosomal plaque at the plasma membrane. ..
  20. Cordi S, Godard C, Saandi T, Jacquemin P, Monga S, Colnot S, et al. Role of β-catenin in development of bile ducts. Differentiation. 2016;91:42-9 pubmed publisher
    ..Our work is expected to significantly impact on in vitro differentiation of stem cells to cholangiocytes for toxicology studies and disease modeling. ..
  21. Birger Y, Davis J, Furusawa T, Rand E, Piatigorsky J, Bustin M. A role for chromosomal protein HMGN1 in corneal maturation. Differentiation. 2006;74:19-29 pubmed
    ..We suggest that interaction of HMGN1 with chromatin modulates the fidelity of gene expression and affects corneal development and maturation. ..
  22. Fausser J, Schlepp O, Aberdam D, Meneguzzi G, Ruch J, Lesot H. Localization of antigens associated with adherens junctions, desmosomes, and hemidesmosomes during murine molar morphogenesis. Differentiation. 1998;63:1-11 pubmed
    ..The specific temporospatial distributions patterns of these antigens suggests a direct involvement of adherens junctions, desmosomes, and hemidesmosomes in the development of the murine first lower molar. ..
  23. Walker J, Menko A, Khalil S, Rebustini I, Hoffman M, Kreidberg J, et al. Diverse roles of E-cadherin in the morphogenesis of the submandibular gland: insights into the formation of acinar and ductal structures. Dev Dyn. 2008;237:3128-41 pubmed publisher
  24. Ohsugi M, Larue L, Schwarz H, Kemler R. Cell-junctional and cytoskeletal organization in mouse blastocysts lacking E-cadherin. Dev Biol. 1997;185:261-71 pubmed
  25. Choy L, Yeo J, Tse V, Chan S, Tse G. Cardiac disease and arrhythmogenesis: Mechanistic insights from mouse models. Int J Cardiol Heart Vasc. 2016;12:1-10 pubmed
    ..Mouse models can serve as useful systems in which to explore how protein defects contribute to arrhythmias and direct future therapy. ..
  26. Koch U, Wilson A, Cobas M, Kemler R, MacDonald H, Radtke F. Simultaneous loss of beta- and gamma-catenin does not perturb hematopoiesis or lymphopoiesis. Blood. 2008;111:160-4 pubmed
    ..These results exclude an essential role for canonical Wnt signaling (as mediated by beta- and/or gamma-catenin) during hematopoiesis and lymphopoiesis. ..
  27. Gustafson Wagner E, Sinn H, Chen Y, Wang D, Reiter R, Lin J, et al. Loss of mXinalpha, an intercalated disk protein, results in cardiac hypertrophy and cardiomyopathy with conduction defects. Am J Physiol Heart Circ Physiol. 2007;293:H2680-92 pubmed
    ..The mXinalpha-knockout mouse line provides a novel model of cardiac hypertrophy and cardiomyopathy with conduction defects. ..
  28. Besco J, Hooft van Huijsduijnen R, Frostholm A, Rotter A. Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT). Brain Res. 2006;1116:50-7 pubmed
    ..proteins in brain, including E-cadherin, N-cadherin, VE-cadherin (cadherin-5), desmoglein, alpha, beta and gamma catenin, p120(ctn) and alpha-actinin...
  29. Bierkamp C, Schwarz H, Huber O, Kemler R. Desmosomal localization of beta-catenin in the skin of plakoglobin null-mutant mice. Development. 1999;126:371-81 pubmed
    ..Our analysis underlines the central role of plakoglobin for desmosomal assembly and function during embryogenesis. ..
  30. Mahendram S, Kelly K, Paez Parent S, Mahmood S, Polena E, Cooney A, et al. Ectopic ?-catenin expression partially mimics the effects of stabilized ?-catenin on embryonic stem cell differentiation. PLoS ONE. 2013;8:e65320 pubmed publisher
    ..Collectively, our study reveals a function for ?-catenin in the regulation of mESC differentiation and has implications for human cancers in which ?-catenin is mutated and/or aberrantly expressed. ..
  31. Pashmforoush M, Pomies P, Peterson K, Kubalak S, Ross J, Hefti A, et al. Adult mice deficient in actinin-associated LIM-domain protein reveal a developmental pathway for right ventricular cardiomyopathy. Nat Med. 2001;7:591-7 pubmed
    ..Taken together, these studies point to a novel developmental pathway for RV dilated cardiomyopathy via instability of alpha-actinin complexes. ..
  32. Cam Y, Fausser J, Vonesch J, Peterkova R, Peterka M, Halaskova M, et al. Asymmetrical morphogenesis and medio-lateral positioning of molars during mouse development. Eur J Oral Sci. 2002;110:35-43 pubmed
  33. Richardson R, Mitchell K, Hammond N, Mollo M, Kouwenhoven E, Wyatt N, et al. p63 exerts spatio-temporal control of palatal epithelial cell fate to prevent cleft palate. PLoS Genet. 2017;13:e1006828 pubmed publisher
  34. Holen I, Whitworth J, Nutter F, Evans A, Brown H, Lefley D, et al. Loss of plakoglobin promotes decreased cell-cell contact, increased invasion, and breast cancer cell dissemination in vivo. Breast Cancer Res. 2012;14:R86 pubmed
    ..This is the first demonstration of a functional role for plakoglobin/?-catenin in the metastatic process, indicating that this molecule may represent a target for antimetastatic therapies. ..
  35. Wickline E, Awuah P, Behari J, Ross M, Stolz D, Monga S. Hepatocyte ?-catenin compensates for conditionally deleted ?-catenin at adherens junctions. J Hepatol. 2011;55:1256-62 pubmed publisher
    ..Catenin adequately maintains AJ in the absence of ?-catenin in hepatocytes; however, it lacks nuclear localization. Moreover, ?-catenin/claudin-2 may be an important mechanism of crosstalk between the AJ and TJ. ..
  36. Li D, Liu Y, Maruyama M, Zhu W, Chen H, Zhang W, et al. Restrictive loss of plakoglobin in cardiomyocytes leads to arrhythmogenic cardiomyopathy. Hum Mol Genet. 2011;20:4582-96 pubmed publisher
    ..A homozygous loss-of-function mutation of the Plakoglobin (Jup) gene, which encodes a major component of the desmosome and the adherens junction, had been identified in Naxos ..
  37. Demireva E, Shapiro L, Jessell T, Zampieri N. Motor neuron position and topographic order imposed by ?- and ?-catenin activities. Cell. 2011;147:641-52 pubmed publisher
    ..These findings reveal that cadherin-catenin signaling directs motor pool patterning and imposes topographic order on an underlying identity-based neural map. ..
  38. Swope D, Cheng L, Gao E, Li J, Radice G. Loss of cadherin-binding proteins ?-catenin and plakoglobin in the heart leads to gap junction remodeling and arrhythmogenesis. Mol Cell Biol. 2012;32:1056-67 pubmed publisher
    ..of ARVC patients have a mutation in genes encoding cell adhesion proteins of the desmosome, including plakoglobin (JUP)...
  39. Tan X, Yuan Y, Zeng G, Apte U, Thompson M, Cieply B, et al. Beta-catenin deletion in hepatoblasts disrupts hepatic morphogenesis and survival during mouse development. Hepatology. 2008;47:1667-79 pubmed publisher
    ..Beta-catenin regulates multiple, critical events during the process of hepatic morphogenesis, including hepatoblast maturation, expansion, and survival, making it indispensable to survival. ..
  40. Kirchhof P, Fabritz L, Zwiener M, Witt H, Schäfers M, Zellerhoff S, et al. Age- and training-dependent development of arrhythmogenic right ventricular cardiomyopathy in heterozygous plakoglobin-deficient mice. Circulation. 2006;114:1799-806 pubmed
    ..Heterozygous plakoglobin deficiency provokes ARVC. Manifestation of the phenotype is accelerated by endurance training. This suggests a functional role for plakoglobin and training in the development of ARVC. ..
  41. Arnemann J, Spurr N, Wheeler G, Parker A, Buxton R. Chromosomal assignment of the human genes coding for the major proteins of the desmosome junction, desmoglein DGI (DSG), desmocollins DGII/III (DSC), desmoplakins DPI/II (DSP), and plakoglobin DPIII (JUP). Genomics. 1991;10:640-5 pubmed
    ..From these data we were able to assign DGI to chromosome 18 (DSG), DGII/III to chromosome 9p (DSC), DPI/II to chromosome 6p21-ter(DSP), and DPIII to chromosome 7 (JUP).
  42. Acehan D, Petzold C, Gumper I, Sabatini D, Muller E, Cowin P, et al. Plakoglobin is required for effective intermediate filament anchorage to desmosomes. J Invest Dermatol. 2008;128:2665-75 pubmed publisher
  43. Jeannet G, Scheller M, Scarpellino L, Duboux S, Gardiol N, Back J, et al. Long-term, multilineage hematopoiesis occurs in the combined absence of beta-catenin and gamma-catenin. Blood. 2008;111:142-9 pubmed
    ..These data provide the first evidence that hematopoietic cells can transduce canonical Wnt signals in the combined absence of beta- and gamma-catenin. ..
  44. Nguyen V, Chernyavsky A, Arredondo J, Bercovich D, Orr Urtreger A, Vetter D, et al. Synergistic control of keratinocyte adhesion through muscarinic and nicotinic acetylcholine receptor subtypes. Exp Cell Res. 2004;294:534-49 pubmed
    ..These findings may aid in the development of novel methods useful for the treatment of skin adhesion diseases and tumor metastasis. ..
  45. Hatsell S, Medina L, Merola J, Haltiwanger R, Cowin P. Plakoglobin is O-glycosylated close to the N-terminal destruction box. J Biol Chem. 2003;278:37745-52 pubmed
    ..This finding has potential implications for understanding the roles of plakoglobin. ..
  46. Swope D, Li J, Muller E, Radice G. Analysis of a Jup hypomorphic allele reveals a critical threshold for postnatal viability. Genesis. 2012;50:717-27 pubmed publisher
    Mutations in the human Jup gene cause arrhythmogenic right ventricular cardiomyopathy (ARVC), a heart muscle disease that often leads to sudden cardiac death...
  47. Kieffer Combeau S, Meyer J, Lesot H. Cell-matrix interactions and cell-cell junctions during epithelial histo-morphogenesis in the developing mouse incisor. Int J Dev Biol. 2001;45:733-42 pubmed
    ..Apoptosis was transiently observed in the contiguous mesenchyme. This affected osteoblasts and also nerve cells close to the labial part of the cervical loop. ..
  48. Tokonzaba E, Chen J, Cheng X, Den Z, Ganeshan R, Muller E, et al. Plakoglobin as a regulator of desmocollin gene expression. J Invest Dermatol. 2013;133:2732-2740 pubmed publisher
    ..It is tempting to speculate that this shift is required for the invasive growth of placode keratinocytes into the dermis, a crucial step in skin appendage formation. ..
  49. Charpentier E, Lavker R, Acquista E, Cowin P. Plakoglobin suppresses epithelial proliferation and hair growth in vivo. J Cell Biol. 2000;149:503-20 pubmed
    ..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. ..
  50. Kant S, Krusche C, Gaertner A, Milting H, Leube R. Loss of plakoglobin immunoreactivity in intercalated discs in arrhythmogenic right ventricular cardiomyopathy: protein mislocalization versus epitope masking. Cardiovasc Res. 2016;109:260-71 pubmed publisher
    ..Reduced plakoglobin staining in intercalated discs of heart tissue from human ARVC patients and in a murine ARVC model is caused by alterations in epitope accessibility and not by protein relocalization. ..
  51. Cifuentes Diaz C, Goudou D, Mege R, Velasco E, Nicolet M, Herrenknecht K, et al. Distinct location and prevalence of alpha-, beta-catenins and gamma-catenin/plakoglobin in developing and denervated skeletal muscle. Cell Adhes Commun. 1998;5:161-76 pubmed
  52. Peifer M, McCrea P, Green K, Wieschaus E, Gumbiner B. The vertebrate adhesive junction proteins beta-catenin and plakoglobin and the Drosophila segment polarity gene armadillo form a multigene family with similar properties. J Cell Biol. 1992;118:681-91 pubmed
    ..The implications of these results for the structure and function of different cell-cell adhesive junctions are discussed. ..