gamma catenin


Summary: A multi-functional catenin that is highly homologous to BETA CATENIN. Gamma catenin binds CADHERINS and helps link their cytoplasmic tails to ACTIN in the CYTOSKELETON via ALPHA CATENIN. It is also found in DESMOSOMES where it mediates the link between DESMOSOMAL CADHERINS and DESMOPLAKIN.

Top Publications

  1. Swope D, Li J, Radice G. Beyond cell adhesion: the role of armadillo proteins in the heart. Cell Signal. 2013;25:93-100 pubmed publisher
    ..This review will discuss the connection between altered cell adhesion and gene expression and its contribution to disease pathogenesis. ..
  2. Lorch J, Klessner J, Park J, Getsios S, Wu Y, Stack M, et al. Epidermal growth factor receptor inhibition promotes desmosome assembly and strengthens intercellular adhesion in squamous cell carcinoma cells. J Biol Chem. 2004;279:37191-200 pubmed
    ..Our results suggest that EGFR inhibition promotes desmosome assembly in oral squamous cell carcinoma cells, resulting in increased cell-cell adhesion. ..
  3. Zhurinsky J, Shtutman M, Ben Ze ev A. Differential mechanisms of LEF/TCF family-dependent transcriptional activation by beta-catenin and plakoglobin. Mol Cell Biol. 2000;20:4238-52 pubmed
    ..These results suggest that overexpression of plakoglobin does not directly activate transcription and that formation of catenin-LEF-DNA complexes is negatively regulated by the catenin N- and C-terminal domains. ..
  4. 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
  5. Pan H, Gao F, Papageorgis P, Abdolmaleky H, Faller D, Thiagalingam S. Aberrant activation of gamma-catenin promotes genomic instability and oncogenic effects during tumor progression. Cancer Biol Ther. 2007;6:1638-43 pubmed
    ..In conclusion, our studies provide a molecular basis for the promotion of genomic instability and the oncogenic effects due to overexpression of gamma-catenin in human cancer. ..
  6. 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. ..
  7. Peifer M, Wieschaus E. The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin. Cell. 1990;63:1167-76 pubmed
    ..We present a possible model for the cellular role of arm. ..
  8. 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. ..
  9. Marcozzi C, Burdett I, Buxton R, Magee A. Coexpression of both types of desmosomal cadherin and plakoglobin confers strong intercellular adhesion. J Cell Sci. 1998;111 ( Pt 4):495-509 pubmed
    ..Plakoglobin may function by potentiating dimer formation, accretion of dimers to cell-cell contact sites or desmosomal cadherin stability. ..

More Information


  1. Yoon J, Kita Y, Frank D, Majewski R, Konicek B, Nobrega M, et al. Gene expression profiling leads to identification of GLI1-binding elements in target genes and a role for multiple downstream pathways in GLI1-induced cell transformation. J Biol Chem. 2002;277:5548-55 pubmed
    ..Many of the GLI1 targets with known function identified in this study increase cell proliferation, indicating that GLI1-induced cell transformation occurs through multiple downstream pathways. ..
  2. 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. ..
  3. 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. ..
  4. Hatzfeld M, Kristjansson G, Plessmann U, Weber K. Band 6 protein, a major constituent of desmosomes from stratified epithelia, is a novel member of the armadillo multigene family. J Cell Sci. 1994;107 ( Pt 8):2259-70 pubmed
    ..The amino-terminal region of B6P (residues 1 to 263) shows no significant homology to any known protein sequence. It may therefore be involved in unique functions of B6P. ..
  5. 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. ..
  6. Todorovic V, Desai B, Eigenheer R, Yin T, Amargo E, Mrksich M, et al. Detection of differentially expressed basal cell proteins by mass spectrometry. Mol Cell Proteomics. 2010;9:351-61 pubmed publisher
  7. Kowalczyk A, Palka H, Luu H, Nilles L, Anderson J, Wheelock M, et al. Posttranslational regulation of plakoglobin expression. Influence of the desmosomal cadherins on plakoglobin metabolic stability. J Biol Chem. 1994;269:31214-23 pubmed
    ..These results demonstrate that the desmosomal cadherins posttranslationally regulate plakoglobin expression by decreasing the rate of plakoglobin degradation. ..
  8. Hoschuetzky H, Aberle H, Kemler R. Beta-catenin mediates the interaction of the cadherin-catenin complex with epidermal growth factor receptor. J Cell Biol. 1994;127:1375-80 pubmed
    ..This interaction is mediated by the evolutionarily conserved central "core" region of beta-catenin. These results suggest that catenins represent an important link between EGF-induced signal transduction and cadherin function. ..
  9. 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
    ..This novel model of ARVC demonstrates for the first time how plakoglobin affects ?-catenin activity in the heart and its implications for disease pathogenesis. ..
  10. 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. ..
  11. 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. ..
  12. Ben Ze ev A, Geiger B. Differential molecular interactions of beta-catenin and plakoglobin in adhesion, signaling and cancer. Curr Opin Cell Biol. 1998;10:629-39 pubmed
  13. Lombardi R, da Graça Cabreira Hansen M, Bell A, Fromm R, Willerson J, Marian A. Nuclear plakoglobin is essential for differentiation of cardiac progenitor cells to adipocytes in arrhythmogenic right ventricular cardiomyopathy. Circ Res. 2011;109:1342-53 pubmed publisher
    ..Nuclear PG provokes adipogenesis in c-Kit+ CPCs by repressing the canonical Wnt signaling and inducing a proadipogenic gene expression. The findings suggest that adipocytes in ARVC, at least in part, originate from c-Kit+ CPCs. ..
  14. Franzen C, Todorovic V, Desai B, Mirzoeva S, Yang X, Green K, et al. The desmosomal armadillo protein plakoglobin regulates prostate cancer cell adhesion and motility through vitronectin-dependent Src signaling. PLoS ONE. 2012;7:e42132 pubmed publisher
  15. Troyanovsky S, Eshkind L, Troyanovsky R, Leube R, Franke W. Contributions of cytoplasmic domains of desmosomal cadherins to desmosome assembly and intermediate filament anchorage. Cell. 1993;72:561-74 pubmed
  16. Shiina H, Breault J, Basset W, Enokida H, Urakami S, Li L, et al. Functional Loss of the gamma-catenin gene through epigenetic and genetic pathways in human prostate cancer. Cancer Res. 2005;65:2130-8 pubmed
    ..The gamma-catenin mutation related to Bcl-2 overexpression has a significant effect on the pathogenesis of HRPC. This is the first report to characterize the epigenetic and genetic regulation of gamma-catenin in human prostate cancer. ..
  17. Muller Tidow C, Steffen B, Cauvet T, Tickenbrock L, Ji P, Diederichs S, et al. Translocation products in acute myeloid leukemia activate the Wnt signaling pathway in hematopoietic cells. Mol Cell Biol. 2004;24:2890-904 pubmed
    ..These data provide evidence that activation of Wnt signaling is a common feature of several balanced translocations in AML. ..
  18. Miravet S, Piedra J, Miro F, Itarte E, Garcia de Herreros A, Duñach M. The transcriptional factor Tcf-4 contains different binding sites for beta-catenin and plakoglobin. J Biol Chem. 2002;277:1884-91 pubmed
    ..These results indicate that Tcf-4 contains two different sites for binding of beta-catenin and plakoglobin, and the interaction of the latter hinders the transcriptional activity of the complex. ..
  19. Sacco P, McGranahan T, Wheelock M, Johnson K. Identification of plakoglobin domains required for association with N-cadherin and alpha-catenin. J Biol Chem. 1995;270:20201-6 pubmed
    ..Plakoglobin is an armadillo family member containing 13 weakly similar internal repeats. These data show that the alpha-catenin-binding region maps within the first repeat and the N-cadherin-binding region maps within repeats 7 and 8. ..
  20. 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
  21. Conacci Sorrell M, Ben Yedidia T, Shtutman M, Feinstein E, Einat P, Ben Ze ev A. Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis. Genes Dev. 2002;16:2058-72 pubmed
    ..The results indicate that induction of Nr-CAM transcription by beta-catenin or plakoglobin plays a role in melanoma and colon cancer tumorigenesis, probably by promoting cell growth and motility. ..
  22. McCrea P, Turck C, Gumbiner B. A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science. 1991;254:1359-61 pubmed
    ..Armadillo plakoglobin may link E-cadherin to the underlying actin cytoskeleton at cell-cell junctions; the E-cadherin-catenin protein complex may also participate in the transmission of developmental information. ..
  23. Chitaev N, Troyanovsky S. Direct Ca2+-dependent heterophilic interaction between desmosomal cadherins, desmoglein and desmocollin, contributes to cell-cell adhesion. J Cell Biol. 1997;138:193-201 pubmed
    ..The observed specific coimmunoprecipitation of MPg by anti-Dsc antibodies in coculture indicates that an intercellular interaction between Dsc1 and Dsg is involved in cell-cell adhesion. ..
  24. Aberle H, Butz S, Stappert J, Weissig H, Kemler R, Hoschuetzky H. Assembly of the cadherin-catenin complex in vitro with recombinant proteins. J Cell Sci. 1994;107 ( Pt 12):3655-63 pubmed
    ..The reconstitution in vitro of the cadherin-catenin complex should allow the study of the interaction with signalling molecules and with the actin-based cytoskeleton. ..
  25. Mathur M, Goodwin L, Cowin P. Interactions of the cytoplasmic domain of the desmosomal cadherin Dsg1 with plakoglobin. J Biol Chem. 1994;269:14075-80 pubmed
    ..This region of Dsg1 sequence shows significant similarity to the catenin-binding domain of classical cadherins, suggesting a common mechanism for the association of plakoglobin with desmosomes and adherens junctions. ..
  26. Tonks A, Pearn L, Musson M, Gilkes A, Mills K, Burnett A, et al. Transcriptional dysregulation mediated by RUNX1-RUNX1T1 in normal human progenitor cells and in acute myeloid leukaemia. Leukemia. 2007;21:2495-505 pubmed
    ..These data provide the most comprehensive and pertinent assessment of the effect of RUNX1-RUNX1T1 on gene expression and demonstrate the highly context-dependent effects of this fusion gene. ..
  27. de Leeuw W, Berx G, Vos C, Peterse J, van de Vijver M, Litvinov S, et al. Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ. J Pathol. 1997;183:404-11 pubmed
    ..Events additional to E-cadherin inactivation must be involved in the transition of lobular carcinoma in situ to invasive lobular carcinoma. ..
  28. Garcia Gras E, Lombardi R, Giocondo M, Willerson J, Schneider M, Khoury D, et al. Suppression of canonical Wnt/beta-catenin signaling by nuclear plakoglobin recapitulates phenotype of arrhythmogenic right ventricular cardiomyopathy. J Clin Invest. 2006;116:2012-21 pubmed
    ..These findings could provide for the opportunity to identify new diagnostic markers and therapeutic targets in patients with ARVC. ..
  29. Gehmlich K, Asimaki A, Cahill T, Ehler E, Syrris P, Zachara E, et al. Novel missense mutations in exon 15 of desmoglein-2: role of the intracellular cadherin segment in arrhythmogenic right ventricular cardiomyopathy?. Heart Rhythm. 2010;7:1446-53 pubmed publisher
  30. Misaki K, Marukawa K, Hayashi Y, Fukusato T, Minamoto T, Hasegawa M, et al. Correlation of gamma-catenin expression with good prognosis in medulloblastomas. J Neurosurg. 2005;102:197-206 pubmed
    ..Expression of gamma-catenin is of great prognostic value and its immunohistochemistry may be useful for further stratification of treatment. Cyclin D expression may have the potential to be an adverse prognostic indicator. ..
  31. Caca K, Kolligs F, Ji X, Hayes M, Qian J, Yahanda A, et al. Beta- and gamma-catenin mutations, but not E-cadherin inactivation, underlie T-cell factor/lymphoid enhancer factor transcriptional deregulation in gastric and pancreatic cancer. Cell Growth Differ. 1999;10:369-76 pubmed
    ..Furthermore, these data imply that the consequences of APC and beta-cat mutations are distinct from the effects of E-cad inactivation. ..
  32. Shibata T, Gotoh M, Ochiai A, Hirohashi S. Association of plakoglobin with APC, a tumor suppressor gene product, and its regulation by tyrosine phosphorylation. Biochem Biophys Res Commun. 1994;203:519-22 pubmed
    ..These results suggest that plakoglobin could play a role in mediating the signals of APC by mutual interaction and that this may be regulated by tyrosine phosphorylation. ..
  33. Ishii K, Norvell S, Bannon L, Amargo E, Pascoe L, Green K. Assembly of desmosomal cadherins into desmosomes is isoform dependent. J Invest Dermatol. 2001;117:26-35 pubmed
    ..Our results demonstrate that desmosome assembly tolerates large shifts in cadherin stoichiometry, but is sensitive to isoform-specific differences exhibited by desmogleins and desmocollins. ..
  34. Papagerakis S, Shabana A, Depondt J, Pibouin L, Blin Wakkach C, Berdal A. Altered plakoglobin expression at mRNA and protein levels correlates with clinical outcome in patients with oropharynx squamous carcinomas. Hum Pathol. 2004;35:75-85 pubmed
    ..The study also shows evidence that the level of expression and intracellular localization of plakoglobin may be useful in predicting the course of disease in patients with oropharyngeal SCC. ..
  35. Gosavi P, Kundu S, Khapare N, Sehgal L, Karkhanis M, Dalal S. E-cadherin and plakoglobin recruit plakophilin3 to the cell border to initiate desmosome assembly. Cell Mol Life Sci. 2011;68:1439-54 pubmed publisher
    ..The results reported here are consistent with the model that PG and E-cadherin recruit PKP3 to the cell border to initiate desmosome formation. ..
  36. Delva E, Tucker D, Kowalczyk A. The desmosome. Cold Spring Harb Perspect Biol. 2009;1:a002543 pubmed publisher
    ..This article outlines the structure and function of the major desmosomal proteins, and explores the contributions of this protein complex to tissue architecture and morphogenesis...
  37. Fuchs M, Muller T, Lerch M, Ullrich A. Association of human protein-tyrosine phosphatase kappa with members of the armadillo family. J Biol Chem. 1996;271:16712-9 pubmed
  38. 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. ..
  39. Kowalczyk A, Bornslaeger E, Borgwardt J, Palka H, Dhaliwal A, Corcoran C, et al. The amino-terminal domain of desmoplakin binds to plakoglobin and clusters desmosomal cadherin-plakoglobin complexes. J Cell Biol. 1997;139:773-84 pubmed
    ..These results identify a role for desmoplakin in organizing the desmosomal cadherin-plakoglobin complex and provide new insights into the hierarchy of protein interactions that occur in the desmosomal plaque. ..
  40. Hawcroft G, D Amico M, Albanese C, Markham A, Pestell R, Hull M. Indomethacin induces differential expression of beta-catenin, gamma-catenin and T-cell factor target genes in human colorectal cancer cells. Carcinogenesis. 2002;23:107-14 pubmed
    ..Differential expression of TCF target genes following indomethacin treatment implies complex effects on multiple genes which play an important role in colorectal carcinogenesis. ..
  41. 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. ..
  42. Morita N, Uemura H, Tsumatani K, Cho M, Hirao Y, Okajima E, et al. E-cadherin and alpha-, beta- and gamma-catenin expression in prostate cancers: correlation with tumour invasion. Br J Cancer. 1999;79:1879-83 pubmed
    ..The data thus suggest that three types of catenin may be useful predictive markers for biological aggressiveness of prostate cancer. ..
  43. Zhurinsky J, Shtutman M, Ben Ze ev A. Plakoglobin and beta-catenin: protein interactions, regulation and biological roles. J Cell Sci. 2000;113 ( Pt 18):3127-39 pubmed
    ..The functional difference between catenins is reflected in their differential involvement in embryonic development and cancer progression. ..
  44. Gillett C, Miles D, Ryder K, Skilton D, Liebman R, Springall R, et al. Retention of the expression of E-cadherin and catenins is associated with shorter survival in grade III ductal carcinoma of the breast. J Pathol. 2001;193:433-41 pubmed
    ..Taken together, these findings suggest that a conserved E-cadherin/catenin axis may play a part in determining adverse outcome in grade III breast carcinoma. ..
  45. Fouquet B, Zimbelmann R, Franke W. Identification of plakoglobin in oocytes and early embryos of Xenopus laevis: maternal expression of a gene encoding a junctional plaque protein. Differentiation. 1992;51:187-94 pubmed
  46. Chidgey M, Dawson C. Desmosomes: a role in cancer?. Br J Cancer. 2007;96:1783-7 pubmed
    ..Loss of desmosomal adhesion is a prerequisite for the epithelial-mesenchymal transition, implicated in the conversion of early stage tumours to invasive cancers...
  47. Asimaki A, Syrris P, Wichter T, Matthias P, Saffitz J, McKenna W. A novel dominant mutation in plakoglobin causes arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet. 2007;81:964-73 pubmed
    ..These results implicate novel molecular mechanisms in the pathogenesis of ARVC...
  48. Lombardi R, Dong J, Rodriguez G, Bell A, Leung T, Schwartz R, et al. Genetic fate mapping identifies second heart field progenitor cells as a source of adipocytes in arrhythmogenic right ventricular cardiomyopathy. Circ Res. 2009;104:1076-84 pubmed publisher
  49. Hinck L, Nathke I, Papkoff J, Nelson W. Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly. J Cell Biol. 1994;125:1327-40 pubmed
    ..Subsequently, > 90% of labeled cadherin, but no additional labeled catenin complexes, entered the TX-100-insoluble fraction.(ABSTRACT TRUNCATED AT 400 WORDS) ..
  50. Smith E, Fuchs E. Defining the interactions between intermediate filaments and desmosomes. J Cell Biol. 1998;141:1229-41 pubmed
    ..As epidermal cells differentiate, PP1 is added as a molecular reinforcement to the plaque, enhancing anchorage to IFs and accounting at least partially for the increase in numbers and stability of desmosomes in suprabasal cells. ..
  51. Fukunaga Y, Liu H, Shimizu M, Komiya S, Kawasuji M, Nagafuchi A. Defining the roles of beta-catenin and plakoglobin in cell-cell adhesion: isolation of beta-catenin/plakoglobin-deficient F9 cells. Cell Struct Funct. 2005;30:25-34 pubmed
    ..Moreover it was suggested that beta-catenin or plakoglobin is required not only for the cell adhesion activity but also for the stable expression and cell surface localization of E-cadherin. ..
  52. Cheng X, Koch P. In vivo function of desmosomes. J Dermatol. 2004;31:171-87 pubmed
  53. Gloushankova N, Wakatsuki T, Troyanovsky R, Elson E, Troyanovsky S. Continual assembly of desmosomes within stable intercellular contacts of epithelial A-431 cells. Cell Tissue Res. 2003;314:399-410 pubmed
    ..Such a diverse range of dynamic activities of desmosomes apparently produces flexible but tight cell-cell adhesion required for different morphogenetic events in epithelial structures. ..