Disease relevance of Involucrin

• Keratinocyte proteins that are expressed in abnormal sites of the epidermis during psoriasis, i.e., keratin 16, filaggrin, and involucrin, were, after PUVA treatment, localized to their normal sites [1].
• Hyperplasia was a result of a disturbed program of epidermal differentiation rather than an increased proliferation rate, as reflected by the strong suppression of keratin 10, involucrin, and loricrin expression in suprabasal cells [2].
• To test the hypothesis that factor VIII expressed in the epidermis can correct hemophilia A, we generated transgenic mice in a factor VIII-deficient background that express human factor VIII under control of the involucrin promoter [3].
• Involucrin accumulation and ionophore-assisted envelope formation, markers of keratinocyte differentiation, were found to be highly dependent on culture conditions in the malignant epidermal keratinocyte line, SCC-13, derived from a human squamous cell carcinoma [4].
• Involucrin, which is incorporated into the cross-linked envelope by the enzyme transglutaminase, was expressed at highest levels in squamous tumors, but several of the non-squamous non-small cell lung carcinoma lines also expressed comparable amounts [5].

High impact information on Involucrin

• We have used the involucrin promoter to express functional human integrin subunits alpha 2, alpha 5, and beta 1 in the suprabasal epidermal layers of transgenic mice [6].
• By comparing the nucleotide sequence of the involucrin gene of the lemur with that of the human, it is clear that the gene has undergone unusual evolution in the primates [7].
• The evolution of involucrin as a substrate of transglutaminase and an envelope precursor was evidently made possible by this process of repeated mutation and duplication [8].
• Enzymatic cross-linking of involucrin and other proteins by keratinocyte particulates in vitro [9].
• In contrast to involucrin, these proteins are associated with membranes [10].

Chemical compound and disease context of Involucrin

• Decreased expression of retinoic acid receptors, transforming growth factor beta, involucrin, and cornifin in cervical intraepithelial neoplasia [11].
• Also, synthesis of epidermal suprabasal keratins (K1 and 10;2D gels) was lower in ORS cultures, but clearly visible suprabasally by immunofluorescence along with other epidermal markers (involucrin, filaggrin, surface glycoprotein gp80, pemphigus vulgaris antigen) [12].
• Sodium dodecyl sulfate caused upregulation of involucrin and downregulation of cytokeratin 1 expression, which is associated with the hyperproliferative/inflammatory epidermal phenotype found in psoriasis, wound healing, and skin irritation [13].
• Basal hyperplasia consisting of involucrin-positive cells was prevalent in prostate tissue from androgen-ablated patients, and formed epithelial clusters flanked by involucrin-negative basal and luminal monolayers [14].
• Both basal cells and suprabasal cell layers of cholesteatoma exhibit an abnormal distribution of differentiation markers (involucrin, filaggrin, glycoproteins detected by monoclonal antibodies J143 [alpha3 integrin chain] and T16 [Trop-2]) [15].

Biological context of Involucrin

• Here we report that when fibronectin is added to the methylcellulose, keratinocytes still withdraw from the cell cycle, but induction of involucrin expression is largely inhibited [16].
• Transgenic mice in which integrins are expressed suprabasally via the involucrin promoter have a sporadic psoriatic phenotype; however, the mechanism by which integrins contribute to the pathogenesis of psoriasis is unknown [17].
• Involucrin synthesis is correlated with cell size in human epidermal cultures [18].
• Cell size and shape become more orderly along the cell migration pathway, and involucrin first appears at some distance from the basal layer, instead of in immediately suprabasal cells, as in the cultured epithelium [19].
• We have analyzed the human involucrin gene in 41 British African-Caribbeans and 37 British white Caucasians by tandem-repeat internal mapping and DNA sequencing [20].

Anatomical context of Involucrin

• Involucrin is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase [8].
• RESULTS: Interferon beta inhibited growth of the NCI-H596 cell line and stimulated envelope competence, involucrin expression, and type 2 transglutaminase activity [21].
• The cells of the basal layer are nearly always free of detectable involucrin, but, in contrast to the natural epithelium, this protein usually makes its appearance in the cells immediately above the basal layer [19].
• This protein, involucrin, is not present in the deepest epithelial cells but appears in the course of their outward migration [19].
• We have generated mice lacking involucrin from embryonic stem cells whose involucrin gene had been ablated by homologous recombination [22].

Associations of Involucrin with other chemical compounds

• Polyacrylamide gel electrophoresis of keratinocyte extracts after this rapid partial purification has revealed in each species tested one (chimpanzee, orangutan, gibbon) or two (gorilla, rhesus, owl, cebus) antigenically crossreactive proteins that migrate in the vicinity of human involucrin [23].
• Moreover, as in nonimmortalized cells, KER-1 involucrin levels are not suppressed by retinoids. trans-Retinoic acid and retinol reduce envelope formation in both nonimmortalized keratinocytes and KER-1 cells [24].
• However, on SLV carrying both involucrin and TGase 1, only five glutamines serve as donors, of which glutamine 496 was the most favored [25].
• Apigenin Inhibition of Involucrin Gene Expression Is Associated with a Specific Reduction in Phosphorylation of Protein Kinase C{delta} Tyr311 [26].
• MMP-9 and the terminal differentiation marker involucrin were co-localized in the same keratinocytes with a high concentration of Ca(2+), a potent stimulator of differentiation [27].

Gene context of Involucrin

• To address this issue, we engineered transgenic mice with desmoglein 3 under the control of the involucrin promoter [28].
• Involucrin promoter-driven SCCA1 transgenic mice showed remarkable resistance against UV irradiation [29].
• To test this hypothesis via a structure-function approach, we generated a tail deletion of Cldn6 (CDelta187) and evaluated its role in epidermal differentiation and EPB formation through its forced expression via the involucrin (Inv) promoter in the suprabasal compartment of the transgenic mouse epidermis [30].
• Involucrin cross-linking by transglutaminase 1. Binding to membranes directs residue specificity [25].
• It is composed of structural proteins, including involucrin, loricrin, and the small proline-rich (SPRR) proteins, all encoded by genes localized at human chromosome 1q21 [31].

Analytical, diagnostic and therapeutic context of Involucrin

• Involucrin, the precursor protein of the cornified cell envelope, could be detected by immunofluorescence only in suprabasal cells [32].
• Of such involucrin-containing keratinocytes, 80% also possessed the potential to undergo DNA synthesis, as determined by autoradiography following a 48-hour incubation with [3H]thymidine [33].
• Using density gradient centrifugation, we were able to isolate a population of small cells containing almost no involucrin, as judged by immunodiffusion, PAGE, and immunoprecipitation [18].
• Immunohistochemistry revealed that the CD44(+) cancer cells have a primitive cellular morphology and costain with the basal cell marker Cytokeratin 5/14, whereas the CD44(-) cancer cells resemble differentiated squamous epithelium and express the differentiation marker Involucrin [34].
• Involucrin appears only in significant quantities in cell culture [35].

References