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Gene Review

IVL  -  involucrin

Homo sapiens

Synonyms: Involucrin
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Disease relevance of IVL


High impact information on IVL


Chemical compound and disease context of IVL


Biological context of IVL


Anatomical context of IVL

  • Involucrin is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase [8].
  • The protein involucrin, synthesized by human keratinocytes, contains 585 amino acids, largely in the form of 10 amino acid repeats, each containing glutamines in 3 conserved positions [20].
  • RESULTS: In human cornea tissue, SPRR1, SPRR2, filaggrin, and involucrin protein expression were detected in the central and peripheral corneal and limbal epithelium [21].
  • The expression vector included an independent transcription unit encoding the aminoglycoside phosphotransferase gene (neo-r) allowing selection of stable involucrin-positive, G418-resistant clonal cell lines [22].
  • We begin by confirming previous observations made in footpad epidermis by showing that the full-length involucrin promoter drives differentiation-appropriate expression in other surface epithelia, including epidermis, cervix, and esophagus [18].

Associations of IVL with chemical compounds


Physical interactions of IVL

  • A 5-base pair (bp) mutation of the AP-1 site (bp --2117 to --2111) within this responsive region abolished CS responsiveness, suggesting a role for the AP-1 complex in the regulation of INV transcription by CS [26].

Regulatory relationships of IVL

  • A signaling cascade that includes protein kinase C (PKC), Ras, and MEKK1 regulates involucrin (hINV) gene expression in epidermal keratinocytes (Efimova, T., LaCelle, P., Welter, J. F., and Eckert, R. L. (1998) J. Biol. Chem. 273, 24387-24395 and Efimova, T., and Eckert, R. L. (2000) J. Biol. Chem. 275, 1601-1607) [16].
  • During terminal differentiation, involucrin becomes covalently cross-linked to other proteins by a membrane-anchored calcium-activated transglutaminase (TG) to form part of the cornified envelope [22].
  • This study shows that overexpression of either YY1 or c-Jun represses transcription of the human involucrin gene in multiplying keratinocytes [27].
  • CONCLUSION: Our study demonstrated for the first time that involucrin expression of keratinocytes is suppressed by RXM through direct inhibition of AP-1 and indirect inhibition of NF-kappaB [2].
  • PI3K inhibitors blocked calcium activation of PLC-gamma1 as well as the induction of keratinocyte differentiation markers involucrin and transglutaminase [28].

Other interactions of IVL

  • By immunogold electron microscopy, this exposed large amounts of involucrin epitopes as well as of desmoplakin, a desmosomal structural protein [29].
  • Here, gel-shift and super-shift assays confirm the binding of LEDGF to the DNA fragments containing HSEs and STREs that are present in the involucrin gene promoter [17].
  • Involucrin expression starts in the upper spinous layers in normal human epidermis and precedes loricrin expression, which is restricted to the granular layer [30].
  • Earlier studies suggested that YY1 and components of the AP-1 family might participate in the silencing of involucrin in proliferating keratinocytes [27].
  • The results with protein pull-down experiments are consistent with the hypothesis that interaction of YY1 with c-Jun is an important mechanism for involucrin repression [27].

Analytical, diagnostic and therapeutic context of IVL


  1. Transglutaminase inhibitors induce hyperproliferation and parakeratosis in tissue-engineered skin. Harrison, C.A., Layton, C.M., Hau, Z., Bullock, A.J., Johnson, T.S., Macneil, S. Br. J. Dermatol. (2007) [Pubmed]
  2. Roxithromycin suppresses involucrin expression by modulation of activator protein-1 and nuclear factor-kappaB activities of keratinocytes. Takahashi, H., Hashimoto, Y., Ishida-Yamamoto, A., Iizuka, H. J. Dermatol. Sci. (2005) [Pubmed]
  3. Terminal differentiation and mitogen-activated protein kinase signaling in human cholesteatoma epithelium. Huisman, M.A., De Heer, E., Grote, J.J. Otol. Neurotol. (2006) [Pubmed]
  4. Expression patterns of loricrin in dermatological disorders. Hohl, D. The American Journal of dermatopathology. (1993) [Pubmed]
  5. A role for mitogen-activated protein kinase activation by integrins in the pathogenesis of psoriasis. Haase, I., Hobbs, R.M., Romero, M.R., Broad, S., Watt, F.M. J. Clin. Invest. (2001) [Pubmed]
  6. Suprabasal integrin expression in the epidermis of transgenic mice results in developmental defects and a phenotype resembling psoriasis. Carroll, J.M., Romero, M.R., Watt, F.M. Cell (1995) [Pubmed]
  7. Remodeling of the involucrin gene during primate evolution. Tseng, H., Green, H. Cell (1988) [Pubmed]
  8. Structure and evolution of the human involucrin gene. Eckert, R.L., Green, H. Cell (1986) [Pubmed]
  9. Enzymatic cross-linking of involucrin and other proteins by keratinocyte particulates in vitro. Simon, M., Green, H. Cell (1985) [Pubmed]
  10. Participation of membrane-associated proteins in the formation of the cross-linked envelope of the keratinocyte. Simon, M., Green, H. Cell (1984) [Pubmed]
  11. Altered expression of immunoreactive involucrin in lamellar ichthyosis. Peña-Penabad, C., de Unamuno, P., García Silva, J., Ludeña, M.D., González Sarmiento, R., Pérez-Arellano, J.L. European journal of dermatology : EJD. (1999) [Pubmed]
  12. Epidermal differentiation characteristics of the psoriatic plaque during short contact treatment with dithranol cream. van der Vleuten, C.J., de Jong, E.M., van de Kerkhof, P.C. Clin. Exp. Dermatol. (1996) [Pubmed]
  13. Decreased expression of retinoic acid receptors, transforming growth factor beta, involucrin, and cornifin in cervical intraepithelial neoplasia. Xu, X.C., Mitchell, M.F., Silva, E., Jetten, A., Lotan, R. Clin. Cancer Res. (1999) [Pubmed]
  14. Hypoxia and differentiation in squamous cell carcinomas of the uterine cervix: pimonidazole and involucrin. Azuma, Y., Chou, S.C., Lininger, R.A., Murphy, B.J., Varia, M.A., Raleigh, J.A. Clin. Cancer Res. (2003) [Pubmed]
  15. Differential effects of detergents on keratinocyte gene expression. van Ruissen, F., Le, M., Carroll, J.M., van der Valk, P.G., Schalkwijk, J. J. Invest. Dermatol. (1998) [Pubmed]
  16. MEK6 regulates human involucrin gene expression via a p38alpha - and p38delta -dependent mechanism. Dashti, S.R., Efimova, T., Eckert, R.L. J. Biol. Chem. (2001) [Pubmed]
  17. Transactivation of involucrin, a marker of differentiation in keratinocytes, by lens epithelium-derived growth factor (LEDGF). Kubo, E., Fatma, N., Sharma, P., Shinohara, T., Chylack, L.T., Akagi, Y., Singh, D.P. J. Mol. Biol. (2002) [Pubmed]
  18. The distal and proximal regulatory regions of the involucrin gene promoter have distinct functions and are required for in vivo involucrin expression. Crish, J.F., Gopalakrishnan, R., Bone, F., Gilliam, A.C., Eckert, R.L. J. Invest. Dermatol. (2006) [Pubmed]
  19. Regulation of involucrin gene expression. Eckert, R.L., Crish, J.F., Efimova, T., Dashti, S.R., Deucher, A., Bone, F., Adhikary, G., Huang, G., Gopalakrishnan, R., Balasubramanian, S. J. Invest. Dermatol. (2004) [Pubmed]
  20. The glutamine residues reactive in transglutaminase-catalyzed cross-linking of involucrin. Simon, M., Green, H. J. Biol. Chem. (1988) [Pubmed]
  21. Expression and regulation of cornified envelope proteins in human corneal epithelium. Tong, L., Corrales, R.M., Chen, Z., Villarreal, A.L., De Paiva, C.S., Beuerman, R., Li, D.Q., Pflugfelder, S.C. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  22. Stable expression of transfected human involucrin gene in various cell types: evidence for in situ cross-linking by type I and type II transglutaminase. Rorke, E.A., Eckert, R.L. J. Invest. Dermatol. (1991) [Pubmed]
  23. Beta ig-h3 induces keratinocyte differentiation via modulation of involucrin and transglutaminase expression through the integrin alpha3beta1 and the phosphatidylinositol 3-kinase/Akt signaling pathway. Oh, J.E., Kook, J.K., Min, B.M. J. Biol. Chem. (2005) [Pubmed]
  24. S100A11, S100A10, annexin I, desmosomal proteins, small proline-rich proteins, plasminogen activator inhibitor-2, and involucrin are components of the cornified envelope of cultured human epidermal keratinocytes. Robinson, N.A., Lapic, S., Welter, J.F., Eckert, R.L. J. Biol. Chem. (1997) [Pubmed]
  25. Cholesterol depletion upregulates involucrin expression in epidermal keratinocytes through activation of p38. Jans, R., Atanasova, G., Jadot, M., Poumay, Y. J. Invest. Dermatol. (2004) [Pubmed]
  26. Cholesterol sulfate stimulates involucrin transcription in keratinocytes by increasing Fra-1, Fra-2, and Jun D. Hanley, K., Wood, L., Ng, D.C., He, S.S., Lau, P., Moser, A., Elias, P.M., Bikle, D.D., Williams, M.L., Feingold, K.R. J. Lipid Res. (2001) [Pubmed]
  27. YY-1 and c-Jun transcription factors participate in the repression of the human involucrin promoter. Alvarez-Salas, L.M., Benitez-Hess, M.L., Dipaolo, J.A. Int. J. Oncol. (2005) [Pubmed]
  28. Calcium-induced human keratinocyte differentiation requires src- and fyn-mediated phosphatidylinositol 3-kinase-dependent activation of phospholipase C-gamma1. Xie, Z., Singleton, P.A., Bourguignon, L.Y., Bikle, D.D. Mol. Biol. Cell (2005) [Pubmed]
  29. Direct evidence that involucrin is a major early isopeptide cross-linked component of the keratinocyte cornified cell envelope. Steinert, P.M., Marekov, L.N. J. Biol. Chem. (1997) [Pubmed]
  30. Analysis of the cornified cell envelope in lamellar ichthyosis. Hohl, D., Huber, M., Frenk, E. Archives of dermatology. (1993) [Pubmed]
  31. Regulation of calprotectin expression by interleukin-1alpha and transforming growth factor-beta in human gingival keratinocytes. Hayashi, N., Kido, J., Kido, R., Wada, C., Kataoka, M., Shinohara, Y., Nagata, T. J. Periodont. Res. (2007) [Pubmed]
  32. Biophysical characterization of involucrin reveals a molecule ideally suited to function as an intermolecular cross-bridge of the keratinocyte cornified envelope. Yaffe, M.B., Beegen, H., Eckert, R.L. J. Biol. Chem. (1992) [Pubmed]
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