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Gene Review

LOR  -  loricrin

Homo sapiens

 
 
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Disease relevance of LOR

 

High impact information on LOR

  • 3. Sequencing of the loricrin gene revealed an insertion that shifts the translation frame of the C-terminal Gly- and Gln/Lys-rich domains, and is likely to impair cornification [4].
  • Radiolabel sequence analysis of cyanogen bromide fragments of p42 led to the conclusion that this antigen is encoded in part by LOR, a conserved portion of the "X" region that is flanked by the envelope gene and the 3' long terminal repeat of HTLV-I [5].
  • Furthermore, in a chemical carcinogen-induced skin carcinogenesis setting, mice overexpressing human IKKalpha in the epidermis under the control of a truncated loricrin promoter developed significantly fewer SCCs and metastases than did wild-type mice [6].
  • 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 [7].
  • Satisfactory features of stratification were obtained, but the expression of epidermal differentiation products, such as keratin K10 and loricrin, was delayed and reduced [8].
 

Chemical compound and disease context of LOR

 

Biological context of LOR

  • Our results demonstrate that loricrin expression is closely linked to an orthokeratotic phenotype of human epidermal keratinization [2].
  • We have previously shown that an AP1 site located in the proximal promoter region (position -55) is essential for human loricrin promoter activity (Rossi, A., Jang, S-I., Ceci, R., Steinert, P. M., and Markova, N. G. (1998) J. Invest. Dermatol. 110, 34-40) [12].
  • NO was also found to inhibit DNA-binding activity of activating protein 1 in keratinocyte nuclear extracts, and to interfere with the transactivation of activating protein 1 responsive genes such as transglutaminase 1, involucrin, and loricrin, whose expression is regulated during epidermal differentiation [13].
  • Sequencing of the loricrin gene has disclosed heterozygous mutations; insertion of one nucleotide (730insG, 709insC) that shifts the reading frame in these patients [14].
  • Elucidation of the molecular biology of "loricrin keratodermas" adds to our understanding of the complexity and biological significance of the CE [14].
 

Anatomical context of LOR

 

Associations of LOR with chemical compounds

  • Involucrin expression starts in the upper spinous layers in normal human epidermis and precedes loricrin expression, which is restricted to the granular layer [20].
  • Subsequently, loricrin becomes cross-linked by the activity of transglutaminases TGK/E as a major component of the cornified cell envelope by N epsilon-(gamma-glutamyl)lysine isopeptide bonds [2].
  • Loricrin is a glycine-, serine-, and cysteine-rich protein expressed very late in epidermal differentiation in the granular layers of normal human epidermis [2].
  • Loricrin, profilaggrin and filaggrin were present in the stratum granulosum of orthokeratinised sites, but expression was abruptly lost at the junction between the vermilion and the intermediate zone [21].
  • Polymerase chain reaction analyses of genomic DNAs from different individuals show that human loricrin consists of two allelic size variants, due to sequence variations in its second glycine loop domain, and these variants segregate in the human population by normal Mendelian mechanisms [22].
 

Enzymatic interactions of LOR

 

Regulatory relationships of LOR

 

Other interactions of LOR

  • Biochemical, structural, and transglutaminase substrate properties of human loricrin, the major epidermal cornified cell envelope protein [16].
  • This rules out the LOR gene as a candidate for the PSORS4 locus [1].
  • SPRR 4, loricrin, and LEP 6 transcripts were not detected [26].
  • In the presence of anti-E-cadherin antibody, both loricrin and profilaggrin levels were dramatically enhanced compared to the high Ca(2+) control cells, while addition of antibody to P-cadherin slightly attenuated the Ca(2+)-induced increase [27].
  • Thus, in undifferentiated cells, loricrin expression is suppressed by Jun B, Sp3, and KSR-1 proteins [12].
 

Analytical, diagnostic and therapeutic context of LOR

  • By use of a specific loricrin antibody, we show by immunogold electron microscopy that loricrin initially appears in the granular layer of human epidermis and forms composite keratohyalin granules with profilaggrin, but localizes to the cell periphery (cell envelope) of fully differentiated stratum corneum cells [22].
  • In control cultures (incubated with no antibody or with antibodies to other cell surface molecules), Ca(2+) elevation induced an increase in type 1 transglutaminase, profilaggrin, and loricrin, as measured by western blotting and in agreement with previous results [27].
  • Immunoelectron microscopy demonstrated that both major cornified cell envelope precursor proteins, involucrin and loricrin, were restricted to the cornified cell envelope in periderm cells at this stage of development [28].
  • Patterns of loricrin and involucrin expression were examined by immunohistochemistry [29].
  • We then measured the steady-state mRNA levels for several S100 genes, small proline rich region-1, -2, and -3, loricrin, and involucrin by Northern blotting [30].

References

  1. Characterization of the loricrin (LOR) gene as a positional candidate for the PSORS4 psoriasis susceptibility locus. Giardina, E., Capon, F., De Rosa, M.C., Mango, R., Zambruno, G., Orecchia, A., Chimenti, S., Giardina, B., Novelli, G. Ann. Hum. Genet. (2004) [Pubmed]
  2. Expression patterns of loricrin in dermatological disorders. Hohl, D. The American Journal of dermatopathology. (1993) [Pubmed]
  3. Structural and functional consequences of loricrin mutations in human loricrin keratoderma (Vohwinkel syndrome with ichthyosis). Schmuth, M., Fluhr, J.W., Crumrine, D.C., Uchida, Y., Hachem, J.P., Behne, M., Moskowitz, D.G., Christiano, A.M., Feingold, K.R., Elias, P.M. J. Invest. Dermatol. (2004) [Pubmed]
  4. A molecular defect in loricrin, the major component of the cornified cell envelope, underlies Vohwinkel's syndrome. Maestrini, E., Monaco, A.P., McGrath, J.A., Ishida-Yamamoto, A., Camisa, C., Hovnanian, A., Weeks, D.E., Lathrop, M., Uitto, J., Christiano, A.M. Nat. Genet. (1996) [Pubmed]
  5. Antigens encoded by the 3'-terminal region of human T-cell leukemia virus: evidence for a functional gene. Lee, T.H., Coligan, J.E., Sodroski, J.G., Haseltine, W.A., Salahuddin, S.Z., Wong-Staal, F., Gallo, R.C., Essex, M. Science (1984) [Pubmed]
  6. A critical role for I{kappa}B kinase {alpha} in the development of human and mouse squamous cell carcinomas. Liu, B., Park, E., Zhu, F., Bustos, T., Liu, J., Shen, J., Fischer, S.M., Hu, Y. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. Abnormal differentiation of epidermis in transgenic mice constitutively expressing cyclooxygenase-2 in skin. Neufang, G., Furstenberger, G., Heidt, M., Marks, F., Müller-Decker, K. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  8. Clues to epidermal cancer proneness revealed by reconstruction of DNA repair-deficient xeroderma pigmentosum skin in vitro. Bernerd, F., Asselineau, D., Vioux, C., Chevallier-Lagente, O., Bouadjar, B., Sarasin, A., Magnaldo, T. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  9. Expression of loricrin is negatively controlled by retinoic acid in human epidermis reconstructed in vitro. Magnaldo, T., Bernerd, F., Asselineau, D., Darmon, M. Differentiation (1992) [Pubmed]
  10. Expression patterns of loricrin in various species and tissues. Hohl, D., Ruf Olano, B., de Viragh, P.A., Huber, M., Detrisac, C.J., Schnyder, U.W., Roop, D.R. Differentiation (1993) [Pubmed]
  11. Comparison of the antiarrhythmic activity of mexiletine and lorcainide on ventricular arrhythmias. Meinertz, T., Kasper, W., Stengel, E., Waldecker, B., Löllgen, H., Jähnchen, E., Bechtold, H., Just, J. Zeitschrift für Kardiologie. (1982) [Pubmed]
  12. Loricrin expression in cultured human keratinocytes is controlled by a complex interplay between transcription factors of the Sp1, CREB, AP1, and AP2 families. Jang, S.I., Steinert, P.M. J. Biol. Chem. (2002) [Pubmed]
  13. Nitric oxide inhibits cornified envelope formation in human keratinocytes by inactivating transglutaminases and activating protein 1. Rossi, A., Catani, M.V., Candi, E., Bernassola, F., Puddu, P., Melino, G. J. Invest. Dermatol. (2000) [Pubmed]
  14. Loricrin and human skin diseases: molecular basis of loricrin keratodermas. Ishida-Yamamoto, A., Takahashi, H., Iizuka, H. Histol. Histopathol. (1998) [Pubmed]
  15. A model for the hierarchical structure of the human epidermal cornified cell envelope. Steinert, P.M. Cell Death Differ. (1995) [Pubmed]
  16. Biochemical, structural, and transglutaminase substrate properties of human loricrin, the major epidermal cornified cell envelope protein. Candi, E., Melino, G., Mei, G., Tarcsa, E., Chung, S.I., Marekov, L.N., Steinert, P.M. J. Biol. Chem. (1995) [Pubmed]
  17. Loricrin keratoderma: a novel disease entity characterized by nuclear accumulation of mutant loricrin. Ishida-Yamamoto, A. J. Dermatol. Sci. (2003) [Pubmed]
  18. Infection with the oncogenic human papillomavirus type 59 alters protein components of the cornified cell envelope. Lehr, E., Brown, D.R. Virology (2003) [Pubmed]
  19. Formation of cornified cell envelope in human hair follicle development. Akiyama, M., Matsuo, I., Shimizu, H. Br. J. Dermatol. (2002) [Pubmed]
  20. Analysis of the cornified cell envelope in lamellar ichthyosis. Hohl, D., Huber, M., Frenk, E. Archives of dermatology. (1993) [Pubmed]
  21. The differentiation profile of the epithelium of the human lip. Barrett, A.W., Morgan, M., Nwaeze, G., Kramer, G., Berkovitz, B.K. Arch. Oral Biol. (2005) [Pubmed]
  22. The human loricrin gene. Yoneda, K., Hohl, D., McBride, O.W., Wang, M., Cehrs, K.U., Idler, W.W., Steinert, P.M. J. Biol. Chem. (1992) [Pubmed]
  23. Short-term retinoic acid treatment increases in vivo, but decreases in vitro, epidermal transglutaminase-K enzyme activity and immunoreactivity. Griffiths, C.E., Rosenthal, D.S., Reddy, A.P., Elder, J.T., Astrom, A., Leach, K., Wang, T.S., Finkel, L.J., Yuspa, S.H., Voorhees, J.J. J. Invest. Dermatol. (1992) [Pubmed]
  24. Temperature-sensitive regulation of epidermal morphogenesis and the expression of cornified envelope precursors by EGF and TGF alpha. Gibbs, S., Boelsma, E., Kempenaar, J., Ponec, M. Cell Tissue Res. (1998) [Pubmed]
  25. Transcription of the human loricrin gene in vitro is induced by calcium and cell density and suppressed by retinoic acid. Hohl, D., Lichti, U., Breitkreutz, D., Steinert, P.M., Roop, D.R. J. Invest. Dermatol. (1991) [Pubmed]
  26. 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]
  27. Inhibition of cadherin function differentially affects markers of terminal differentiation in cultured human keratinocytes. Hines, M.D., Jin, H.C., Wheelock, M.J., Jensen, P.J. J. Cell. Sci. (1999) [Pubmed]
  28. Periderm cells form cornified cell envelope in their regression process during human epidermal development. Akiyama, M., Smith, L.T., Yoneda, K., Holbrook, K.A., Hohl, D., Shimizu, H. J. Invest. Dermatol. (1999) [Pubmed]
  29. Premature apoptosis of keratinocytes and the dysregulation of keratinization in porokeratosis. Shen, C.S., Tabata, K., Matsuki, M., Goto, T., Yokochi, T., Yamanishi, K. Br. J. Dermatol. (2002) [Pubmed]
  30. Evidence for local control of gene expression in the epidermal differentiation complex. Elder, J.T., Zhao, X. Exp. Dermatol. (2002) [Pubmed]
 
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