title: Plakoglobin as a regulator of desmocollin gene expression.
abstract: Desmosomes are cell adhesion junctions required for the normal development and maintenance of mammalian tissues and organs such as the skin, skin appendages, and the heart. The goal of this study was to investigate how desmocollins (DSCs), transmembrane components of desmosomes, are regulated at the transcriptional level. We hypothesized that differential expression of the Dsc2 and Dsc3 genes is a prerequisite for normal development of skin appendages. We demonstrate that plakoglobin (Pg) in conjunction with lymphoid enhancer-binding factor 1 (Lef-1) differentially regulates the proximal promoters of these two genes. Specifically, we found that Lef-1 acts as a switch activating Dsc2 and repressing Dsc3 in the presence of Pg. Interestingly, we also determined that NF-κB pathway components, the downstream effectors of the ectodysplasin-A (EDA)/ ectodysplasin-A receptor (EDAR)/NF-κB signaling cascade, can activate Dsc2 expression. We hypothesize that Lef-1 and EDA/EDAR/NF-κB signaling contribute to a shift in Dsc isoform expression from Dsc3 to Dsc2 in placode keratinocytes. 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.
authors: Department of Dermatology, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors: Etienne
authors: E
authors: Tokonzaba
authors: Department of Dermatology, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors: Jiangli
authors: J
authors: Chen
authors: Department of Dermatology, Baylor College of Medicine, Houston, Texas, USA.
authors: Xing
authors: X
authors: Cheng
authors: Department of Dermatology, Baylor College of Medicine, Houston, Texas, USA.
authors: Zhining
authors: Z
authors: Den
authors: Department of Dermatology, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors: Radhika
authors: R
authors: Ganeshan
authors: Molecular Dermatology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors: Eliane J
authors: EJ
authors: Műller
authors: Department of Dermatology, University of Colorado School of Medicine, Aurora, Colorado, USA; Department of Dermatology, Baylor College of Medicine, Houston, Texas, USA; Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado, USA. Electronic address: Peter.Koch@ucdenver.edu.
authors: Peter J
authors: PJ
authors: Koch
mesh_terms: D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D051187:Desmocollins; D004285:Dogs; D053331:Ectodysplasins / Q000378:metabolism; D005786:Gene Expression Regulation; D015603:Keratinocytes / Q000166:cytology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D053338:Receptors, Ectodysplasin / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D051185:gamma Catenin / Q000502:physiology*
chemical_list: D051187:Desmocollins; C489912:Dsc2 protein, mouse; D053331:Ectodysplasins; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053338:Receptors, Ectodysplasin; D051185:gamma Catenin; C090171:Dsc3 protein, mouse
references: Dev Cell. 2009 Jul;17(1):49-61
references: 19619491
references: J Biol Chem. 2012 Mar 23;287(13):10435-10443
references: 22315228
references: BMC Cancer. 2009 May 21;9:159
references: 19460168
references: Cancer Res. 2002 Oct 15;62(20):5947-54
references: 12384561
references: Mol Cell Biol. 2004 Oct;24(19):8649-61
references: 15367683
references: J Cell Biol. 1997 Jun 2;137(5):1091-102
references: 9166409
references: Mol Cell Biol. 2002 Aug;22(16):5846-58
references: 12138195
references: Mol Carcinog. 2012 Jul;51(7):535-45
references: 21681825
references: Differentiation. 1998 Sep;63(5):295-304
references: 9810708
references: Mol Cell Biol. 2000 Jun;20(12):4238-52
references: 10825188
references: J Invest Dermatol. 2012 Mar;132(3 Pt 2):776-84
references: 22189787
references: Oncogene. 2003 Jun 5;22(23):3624-34
references: 12789271
references: Eur J Cell Biol. 2005 Mar;84(2-3):215-23
references: 15819402
references: Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3299-304
references: 12626757
references: Oncogene. 2004 Jan 29;23(4):964-72
references: 14661054
references: Br J Dermatol. 2012 Jan;166(1):36-45
references: 21929534
references: PLoS One. 2012;7(7):e42132
references: 22860065
references: J Cell Sci. 1998 Sep;111 ( Pt 17):2529-37
references: 9701552
references: J Invest Dermatol. 2008 Mar;128(3):501-16
references: 18268536
references: Cell Signal. 2013 Jan;25(1):93-100
references: 23022961
references: Sci Signal. 2008 Sep 30;1(39):pe43
references: 18827220
references: J Invest Dermatol. 2007 Apr;127(4):792-801
references: 17110936
references: Nature. 2003 Mar 20;422(6929):317-22
references: 12646922
references: Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5420-5
references: 15805189
references: Biochem J. 2004 Jun 15;380(Pt 3):757-65
references: 15030314
references: Dev Growth Differ. 2001 Oct;43(5):535-44
references: 11576170
references: EMBO J. 2006 Jul 26;25(14):3298-309
references: 16871158
references: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3255-60
references: 17360634
references: Mol Cell Biol. 2004 Jan;24(1):154-63
references: 14673151
references: Mech Dev. 1996 Sep;59(1):3-10
references: 8892228
references: J Invest Dermatol. 2000 Jan;114(1):171-7
references: 10620134
references: Dermatol Res Pract. 2010;2010:584353
references: 20585602
references: J Cell Biol. 2001 Apr 30;153(3):555-68
references: 11331306
references: Mol Cell Biol. 2011 Mar;31(6):1134-44
references: 21245375
references: J Cell Biol. 2001 Nov 26;155(5):821-32
references: 11714727
references: Dev Dyn. 1997 Nov;210(3):315-27
references: 9389456
references: Cell Adh Migr. 2007 Jan-Mar;1(1):28-32
references: 19262094
references: J Dermatol. 2004 Mar;31(3):171-87
references: 15187337
references: Breast Cancer Res. 2005;7(5):R669-80
references: 16168112
references: Curr Biol. 2011 Jul 26;21(14):R529-31
references: 21783027
references: Br J Cancer. 2005 Jun 20;92(12):2153-9
references: 15942628
references: Mol Cell Biol. 2005 Feb;25(3):969-78
references: 15657425
references: Int J Oncol. 2001 Jul;19(1):169-74
references: 11408939
references: Development. 2001 Oct;128(19):3843-53
references: 11585809
references: J Cell Sci. 2008 Sep 1;121(Pt 17):2844-9
references: 18682494
references: J Cell Biol. 2001 Apr 16;153(2):243-9
references: 11309406
references: J Cell Biol. 1998 Jun 15;141(6):1433-48
references: 9628899
references: Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1023-7
references: 8430069
references: J Cell Biol. 2000 Oct 16;151(2):389-400
references: 11038185
references: Science. 1997 Mar 21;275(5307):1784-7
references: 9065401