Dermokine: An Extensively Differentially Spliced Gene Expressed in Epithelial Cells

Naso, Michael F.; Liang, Bailin; Huang, Chenlu; Song, Xiaoyu; Shahied-Arruda, Lillian; Belkowski, Stanley M.; D’Andrea, Michael R.; Polkovitch, Debbie A.; Lawrence, Danielle; Griswold, Don E.; Sweet, Ray; Amegadzie, Bernard Y.

doi:10.1038/sj.jid.5700779

Cited by 24 publications

(37 citation statements)

References 13 publications

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“…Dmkn encodes a secreted protein of unknown function that is highly expressed in the spinous and granular layers of stratified epithelia (Matsui et al, 2004) but is also expressed in the gut, lung, breast, liver and pancreas (Naso et al, 2007). The wide expression profile of Dmkn is reminiscent of that for Perp, which is expressed in stratified epithelia as well as in the heart, forestomach, submandibular gland and thymus (Ihrie et al, 2005).…”

Section: Perp and The Regulation Of Gene Expressionmentioning

confidence: 99%

PERP regulates enamel formation via effects on cell–cell adhesion and gene expression

Jheon

Mostowfi

Snead

et al. 2011

Journal of Cell Science

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SummaryLittle is known about the role of cell-cell adhesion in the development of mineralized tissues. Here we report that PERP, a tetraspan membrane protein essential for epithelial integrity, regulates enamel formation. PERP is necessary for proper cell attachment and gene expression during tooth development, and its expression is controlled by P63, a master regulator of stratified epithelial development. During enamel formation, PERP is localized to the interface between the enamel-producing ameloblasts and the stratum intermedium (SI), a layer of cells subjacent to the ameloblasts. Perp-null mice display dramatic enamel defects, which are caused, in part, by the detachment of ameloblasts from the SI. Microarray analysis comparing gene expression in teeth of wild-type and Perp-null mice identified several differentially expressed genes during enamel formation. Analysis of these genes in ameloblast-derived LS8 cells upon knockdown of PERP confirmed the role for PERP in the regulation of gene expression. Together, our data show that PERP is necessary for the integrity of the ameloblast-SI interface and that a lack of Perp causes downregulation of genes that are required for proper enamel formation.

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Section: Perp and The Regulation Of Gene Expressionmentioning

confidence: 99%

PERP regulates enamel formation via effects on cell–cell adhesion and gene expression

Jheon

Mostowfi

Snead

et al. 2011

Journal of Cell Science

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“…2A, exposure of keratinocytes to dermokine-b for 24 h stimulated its gene expression in a dose-dependent manner, whereas no significant change of involucrin expression was observed. A secreted form of dermokine-b consists of amino-terminus globular (Glo1), coiled-coil collagen-like (Coil), keratin-like (Ker), spacer (Spa) and carboxyl-terminus globular domain (Glo2) [6]. To define the active regions of dermokine-b to stimulate its gene expression, dermokine-b deletion mutants were prepared, and incubated with keratinocytes at a dose of 3 lg/ml (Fig.…”

Section: Carboxyl-terminus Domain Of Dermokine-b Exhibits Functional mentioning

confidence: 99%

“…Unlike the c and d isoforms, dermokine-a is also a secreted protein that contains the same carboxyl-terminus globular domain as dermokine-b [4,6]. We and others have suggested that the expressions of both dermokine-b and -a were coordinately regulated [4,9], implying the additional involvement of dermokine-a in keratinocyte differentiation.…”

mentioning

confidence: 99%

“…Northern blotting and quantitative RT-PCR revealed that dermokine is abundant in stratified epithelia and in differentiating primary human keratinocytes [4]. Human dermokine has been reported to be encoded by 25 exons, spanning 17 kb of genomic DNA [4][5][6]. Its expression leads to four groups of transcripts according to three different transcriptional start sites, two termination sites and several alternative coding exons [7].…”

Section: Introductionmentioning

confidence: 99%

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Dermokine‐β impairs ERK signaling through direct binding to GRP78

et al. 2012

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a b s t r a c tDermokine-b is abundant in stratified epithelia and in differentiating cultured keratinocytes. In this study, we investigated the role of dermokine-b in differentiation of keratinocytes. Treatment of keratinocytes or skin tumor cells with dermokine-b attenuated phosphorylation of extracellularsignal-regulated kinase (ERK). Exposure of cells to dermokine-b, as well as its carboxyl-terminus domain peptide, interrupted phosphorylation of ERK and stimulated dermokine gene expression. Inhibition of ERK signaling by its specific inhibitor also increased dermokine expression level. A combination of chemical cross-linking and immunoprecipitation, followed by proteomics analyses, identified glucose-regulated protein 78 (GRP78) as a dermokine-b-associated protein. Blockage of GRP78 expression by a specific siRNA abrogated actions of dermokine-b. These findings provide novel insights into the physiological significance of dermokine-b in the epidermis.

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“…The mouse SSC locus displays the same genomic organization as that of humans, with Sbsn and Krtdap flanking Dmkn, in the same orientation. Dmkn spans 22 exons and transcripts belonging to the a, b and c isoforms have been described, but no messengers coding putative d isoforms (Matsui et al, 2004;Moffatt et al, 2004;Naso et al, 2007). Here, we performed an in-depth characterization of the Dmkn transcripts expressed in the mouse skin.…”

Section: Introductionmentioning

confidence: 99%

Mice deficient for the epidermal Dermokine β and γ display transient cornification defects

Leclerc

Huchenq

Kežić

et al. 2014

Journal of Cell Science

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Expression of the human dermokine gene (DMKN) leads to the production of four dermokine isoform families. The secreted a, b and c isoforms have an epidermis-restricted expression pattern, with Dmkn b and c being specifically expressed by the granular keratinocytes. The d isoforms are intracellular and ubiquitous. Here, we performed an in-depth characterization of Dmkn expression in mouse skin and found an expression pattern that was less complex than in humans. In particular, mRNA coding for the d family were absent. Homozygous mice null for the Dmkn b and c isoforms had no obvious phenotype but only a temporary scaly skin during the first week of life. The pups null for the Dmkn b and c isoforms had smaller keratohyalin granules and their cornified envelopes were more sensitive to mechanical stress. At the molecular level, amounts of profilaggrin and filaggrin monomers were reduced whereas amino acid components of the natural moisturizing factor were increased. In addition, the electrophoretic mobility of involucrin was modified, suggesting post-translational modifications. Finally, the mice null for the Dmkn b and c isoforms strongly overexpressed Dmkn a. These data are evocative of compensatory mechanisms relevant to the temporary phenotype. Overall, we improved the knowledge of Dmkn expression in mouse and highlighted a role for Dmkn b and c in cornification.

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Dermokine: An Extensively Differentially Spliced Gene Expressed in Epithelial Cells

Cited by 24 publications

References 13 publications

PERP regulates enamel formation via effects on cell–cell adhesion and gene expression

PERP regulates enamel formation via effects on cell–cell adhesion and gene expression

Dermokine‐β impairs ERK signaling through direct binding to GRP78

Mice deficient for the epidermal Dermokine β and γ display transient cornification defects

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