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Gene Review

Krt1  -  keratin 1

Mus musculus

Synonyms: 67 kDa cytokeratin, CK-1, Cytokeratin-1, K1, Keratin, type II cytoskeletal 1, ...
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Disease relevance of Krt1


High impact information on Krt1

  • To demonstrate function, we engineered one of these point mutations in a cloned human K14 cDNA, and showed that a K14 with an Arg-125----Cys mutation disrupted keratin network formation in transfected keratinocytes and perturbed filament assembly in vitro [5].
  • Since we had previously shown that keratin network perturbation is an essential component of EBS diseases, these data suggest that the basis for the phenotype in this patient resides in this point mutation [5].
  • We now demonstrate that two patients with spontaneous cases of Dowling-Meara EBS have point mutations in a critical region in one (K14) of two basal keratin genes [5].
  • Previously we demonstrated that transgenic mice expressing mutant basal epidermal keratin genes exhibited a phenotype resembling a group of autosomal dominant human skin disorders known as epidermolysis bullosa simplex (EBS) [5].
  • With retrovirus-mediated gene transfer, we used intact and deleted keratin proteins to investigate the molecular basis of intermediate filament function [6].

Chemical compound and disease context of Krt1


Biological context of Krt1


Anatomical context of Krt1

  • Notably, specific 'soft' keratins, Krt2-1 and Krt2-17, normally weakly expressed in the tongue but present at high levels in skin and in orthokeratinized oral dysplasia are up-regulated in the mutant tongue epithelium [15].
  • Transient and stable transfectants, as well as heterokaryons produced by fusions with epithelial cells, were evaluated for expression of K1 and K10 proteins and filament formation using specific antibodies [12].
  • Keratins 1 (K1) and 10 (K10) are the predominant cytoskeletal intermediate filaments of epidermal cells during transition from the proliferative to the terminal differentiation stage [12].
  • The major differentiation products in suprabasal keratinocytes are keratins, K1 and K10 [16].
  • The formation of a recombinant cytoskeleton was more restricted for K10 than for K1 and appeared to be related to a requirement for cessation of cell division before K10 could integrate [17].

Associations of Krt1 with chemical compounds


Physical interactions of Krt1


Enzymatic interactions of Krt1


Co-localisations of Krt1


Regulatory relationships of Krt1


Other interactions of Krt1

  • In situ, formation of the K1/K10 intermediate filament network occurs in the cytoplasm of cells with a preexisting cytoskeleton composed of keratins 5 and 14 [12].
  • The K1/K14 pair was capable of forming a cytoskeletal network, but the network was poorly developed, and usually perinuclear [12].
  • The localization of both K5 and K1 proteins in these same cell layers, and above, is consistent with transcriptional regulation of these keratins [18].
  • High constitutive ODC expression and decreased K1 and K10 expression will be useful phenotypic markers for studying the early stages of tumorigenesis in mouse skin [16].
  • The integration of exogenous K1 filaments into the endogenous keratin network was compatible with sustained proliferation of SLC-1 carcinoma cells in vitro [17].

Analytical, diagnostic and therapeutic context of Krt1


  1. Transcriptional control of high molecular weight keratin gene expression in multistage mouse skin carcinogenesis. Roop, D.R., Krieg, T.M., Mehrel, T., Cheng, C.K., Yuspa, S.H. Cancer Res. (1988) [Pubmed]
  2. Simple assays of retinoid activity as potential screens for compounds that may be useful in treatment of psoriasis. West, M.R., Page, J.M., Turner, D.M., Wood, E.J., Holland, D.B., Cunliffe, W.J., Rupniak, H.T. J. Invest. Dermatol. (1992) [Pubmed]
  3. Aberrant expression of the simple epithelial type II keratin 8 by mouse skin carcinomas but not papillomas. Larcher, F., Bauluz, C., Díaz-Guerra, M., Quintanilla, M., Conti, C.J., Ballestín, C., Jorcano, J.L. Mol. Carcinog. (1992) [Pubmed]
  4. Proteasome inhibition induces cytokeratin accumulation in vivo. Bardag-Gorce, F., Vu, J., Nan, L., Riley, N., Li, J., French, S.W. Exp. Mol. Pathol. (2004) [Pubmed]
  5. Point mutations in human keratin 14 genes of epidermolysis bullosa simplex patients: genetic and functional analyses. Coulombe, P.A., Hutton, M.E., Letai, A., Hebert, A., Paller, A.S., Fuchs, E. Cell (1991) [Pubmed]
  6. Retrovirus-mediated transgenic keratin expression in cultured fibroblasts: specific domain functions in keratin stabilization and filament formation. Lu, X., Lane, E.B. Cell (1990) [Pubmed]
  7. Actin overexpression parallels severity of pancreatic injury. Zhong, B., Omary, M.B. Exp. Cell Res. (2004) [Pubmed]
  8. The proteasome inhibitor, PS-341, causes cytokeratin aggresome formation. Bardag-Gorce, F., Riley, N.E., Nan, L., Montgomery, R.O., Li, J., French, B.A., Lue, Y.H., French, S.W. Exp. Mol. Pathol. (2004) [Pubmed]
  9. Effects of inhibitors of tumor promotion on 12-O-tetradecanoylphorbol-13-acetate-induced keratin modification in mouse epidermis. Nelson, K.G., Slaga, T.J. Carcinogenesis (1982) [Pubmed]
  10. Gene expression changes associated with chemically induced rat mammary carcinogenesis. Lu, J., Pei, H., Kaeck, M., Thompson, H.J. Mol. Carcinog. (1997) [Pubmed]
  11. Selective cyclooxygenase-2 inhibition does not alter keratinocyte wound responses in the mouse epidermis after abrasion. Hardy, M.M., Blomme, E.A., Lisowski, A., Chinn, K.S., Jones, A., Harmon, J.M., Opsahl, A., Ornberg, R.L., Tripp, C.S. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  12. Mouse differentiation-specific keratins 1 and 10 require a preexisting keratin scaffold to form a filament network. Kartasova, T., Roop, D.R., Holbrook, K.A., Yuspa, S.H. J. Cell Biol. (1993) [Pubmed]
  13. Keratin 18 overexpression but not phosphorylation or filament organization blocks mouse Mallory body formation. Harada, M., Strnad, P., Resurreccion, E.Z., Ku, N.O., Omary, M.B. Hepatology (2007) [Pubmed]
  14. Formation of a normal epidermis supported by increased stability of keratins 5 and 14 in keratin 10 null mice. Reichelt, J., Büssow, H., Grund, C., Magin, T.M. Mol. Biol. Cell (2001) [Pubmed]
  15. Pax9 is required for filiform papilla development and suppresses skin-specific differentiation of the mammalian tongue epithelium. Jonker, L., Kist, R., Aw, A., Wappler, I., Peters, H. Mech. Dev. (2004) [Pubmed]
  16. Ornithine decarboxylase expression in cutaneous papillomas in SENCAR mice is associated with altered expression of keratins 1 and 10. Sundberg, J.P., Erickson, A.A., Roop, D.R., Binder, R.L. Cancer Res. (1994) [Pubmed]
  17. Relationship between the expression of differentiation-specific keratins 1 and 10 and cell proliferation in epidermal tumors. Kartasova, T., Roop, D.R., Yuspa, S.H. Mol. Carcinog. (1992) [Pubmed]
  18. Retinoid status controls the appearance of reserve cells and keratin expression in mouse cervical epithelium. Darwiche, N., Celli, G., Sly, L., Lancillotti, F., De Luca, L.M. Cancer Res. (1993) [Pubmed]
  19. Expression of keratins in mouse vaginal epithelium. Gimenez-Conti, I.B., Lynch, M., Roop, D., Bhowmik, S., Majeski, P., Conti, C.J. Differentiation (1994) [Pubmed]
  20. Promotion of skin carcinogenesis by dimethylarsinic acid in keratin (K6)/ODC transgenic mice. Morikawa, T., Wanibuchi, H., Morimura, K., Ogawa, M., Fukushima, S. Jpn. J. Cancer Res. (2000) [Pubmed]
  21. Targeted activation of beta-catenin signaling in basal mammary epithelial cells affects mammary development and leads to hyperplasia. Teulière, J., Faraldo, M.M., Deugnier, M.A., Shtutman, M., Ben-Ze'ev, A., Thiery, J.P., Glukhova, M.A. Development (2005) [Pubmed]
  22. Keratin binding to 14-3-3 proteins modulates keratin filaments and hepatocyte mitotic progression. Ku, N.O., Michie, S., Resurreccion, E.Z., Broome, R.L., Omary, M.B. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  23. One of two Ets-binding sites in the cytokeratin EndoA enhancer is essential for enhancer activity and binds to Ets-2 related proteins. Fujimura, Y., Yamamoto, H., Hamazato, F., Nozaki, M. Nucleic Acids Res. (1994) [Pubmed]
  24. Close linkage of retinoic acid receptor genes with homeobox- and keratin-encoding genes on paralogous segments of mouse chromosomes 11 and 15. Nadeau, J.H., Compton, J.G., Giguère, V., Rossant, J., Varmuza, S. Mamm. Genome (1992) [Pubmed]
  25. IgG binds to desmoglein 3 in desmosomes and causes a desmosomal split without keratin retraction in a pemphigus mouse model. Shimizu, A., Ishiko, A., Ota, T., Tsunoda, K., Amagai, M., Nishikawa, T. J. Invest. Dermatol. (2004) [Pubmed]
  26. Expression of the integrin subunit alpha8 in murine lung development. Wagner, T.E., Frevert, C.W., Herzog, E.L., Schnapp, L.M. J. Histochem. Cytochem. (2003) [Pubmed]
  27. A transglutaminase-related antigen associates with keratin filaments in some mouse epidermal cells. Clement, S., Trejo-Skalli, A.V., Gu, L., Velasco, P.T., Lorand, L., Goldman, R.D. J. Invest. Dermatol. (1997) [Pubmed]
  28. Overexpression of a dominant-negative ornithine decarboxylase in mouse skin: effect on enzyme activity and papilloma formation. Shantz, L.M., Guo, Y., Sawicki, J.A., Pegg, A.E., O'Brien, T.G. Carcinogenesis (2002) [Pubmed]
  29. Low frequency of codon 61 Ha-ras mutations and lack of keratin 13 expression in 7,12-dimethylbenz[a]-anthracene-induced hamster skin tumors. Robles, A.I., Gimenez-Conti, I.B., Roop, D., Slaga, T.J., Conti, C.J. Mol. Carcinog. (1993) [Pubmed]
  30. Impaired NF-kappa B activation and increased production of tumor necrosis factor alpha in transgenic mice expressing keratin K10 in the basal layer of the epidermis. Santos, M., Perez, P., Segrelles, C., Ruiz, S., Jorcano, J.L., Paramio, J.M. J. Biol. Chem. (2003) [Pubmed]
  31. Hair follicle apoptosis and Bcl-2. Müller-Röver, S., Rossiter, H., Lindner, G., Peters, E.M., Kupper, T.S., Paus, R. J. Investig. Dermatol. Symp. Proc. (1999) [Pubmed]
  32. Changes in keratin expression during malignant progression of transformed mouse epidermal keratinocytes. Caulín, C., Bauluz, C., Gandarillas, A., Cano, A., Quintanilla, M. Exp. Cell Res. (1993) [Pubmed]
  33. Characterization of Bsk mice: I. The Bsk mutation does not involve a recombination of cornea-specific keratin 12 and skin-specific hair keratin genes. Shiraishi, A., Kao, C.W., Ishizaki, M., Zhang, Z., Converse, R.L., Tseng, S.C., Svoboda, K.K., Kao, W.W. Curr. Eye Res. (1998) [Pubmed]
  34. Expression of an epidermal keratin protein in liver of transgenic mice causes structural and functional abnormalities. Albers, K.M., Davis, F.E., Perrone, T.N., Lee, E.Y., Liu, Y., Vore, M. J. Cell Biol. (1995) [Pubmed]
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