Disease relevance of Krt10

• In early papillomas, K1 staining was patchy, and K10 staining occurred in very limited focal areas or was negative, such that the absence of staining delineated the lesions [1].
• An unexpected role for keratin 10 end domains in susceptibility to skin cancer [2].
• Transgenic mice expressing a mutant keratin 10 gene reveal the likely genetic basis for epidermolytic hyperkeratosis [3].
• Positive reaction was obtained for CK4, CK34betaE12, CK10, CK14 in skin and cholesteatoma epithelium [4].
• To generate paucibacillary infection, C57BL/6 mice were artificially infected with Mycobacterium avium subsp. paratuberculosis strain K10 and M. tuberculosis H37Rv, yielding tissues harboring fewer than one bacillus per oil immersion field [5].

High impact information on Krt10

• A second form, Skn-1a, contains an alternative amino terminus and serves to activate cytokeratin 10 (K10) gene expression [6].
• Driven by the suprabasal-specific keratin-10 gene promoter, expression of dnRXR alpha severely reduced the ability of RAR-selective ligands tRA and CD367 to induce epidermal mRNA levels of the CRABPII, CRBPI, and CRBPII genes, which contain RA-responsive elements (RAREs) DR1 and/or DR2 [7].
• Transgenic mice were generated using a keratin 10 (K10) gene promoter to drive constitutive expression of TGF-beta 1 in the suprabasal keratinocyte compartment [8].
• This genetic model allows activation of a somatic K10 mutation in epidermal stem cells in a spatially and temporally controlled manner using an inducible Cre recombinase [9].
• We constitutively overexpressed BMP-6 in suprabasal layers of interfollicular epidermis in transgenic mice using a keratin 10 promoter [10].

Biological context of Krt10

• Transfection of K10 in combination with K5 or K1 resulted in cytoplasmic agglomerates, but not a cytoskeleton [11].
• The mild phenotype of K10(-/-) mice suggests that there is a considerable redundancy in the keratin gene family [12].
• Here, we show that the loss of K10, the most prominent epidermal protein, allowed the formation of a normal epidermis in neonatal mice without signs of fragility or wound-healing response [12].
• Furthermore, the ability of K10 to suppress cell proliferation was mapped to its unique N- and C-terminal protein domains [2].
• Unlike most keratin mutant mice, the epidermis of adult K10-/- mice showed no cytolysis but displayed hyperproliferation of basal keratinocytes and an increased cell size [13].

Anatomical context of Krt10

• 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 [11].
• 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 [11].
• The major differentiation products in suprabasal keratinocytes are keratins, K1 and K10 [1].
• Sebaceous gland cells of K10-/- mice showed an accelerated turnover and secreted more sebum including wax esters, triglycerides, and cholesterol esters [14].
• Forced expression of K10, a keratin normally expressed in postmitotic, terminally differentiating epidermal keratinocytes, inhibits the progression of the cell cycle in cultured cells (Paramio, J. M., Casanova, M. Ll., Segrelles, C., Mittnacht, S., Lane, E. B., and Jorcano, J. L. (1999) Mol. Cell. Biol. 19, 3086-3094) [15].

Associations of Krt10 with chemical compounds

• The treatment of basal cells with retinoic acid at pharmacological concentrations prevented the expression of K1 and K10 when cells were challenged by 1.4 mM Ca2+ [16].
• At doses which activate PKC, 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1-oleoyl-2-acetylglycerol block Ca(2+)-mediated induction of the spinous cell markers keratins K1 and K10 at both the protein and mRNA level [17].
• By use of cross-linking, high resolution polyacrylamide gel electrophoresis and blotting for 3H-labeled keratins or with an anti-mouse keratin 10 antibody, it was found that individual keratin chains form type I or type II homodimers and homotetramers in solution that do not assemble into KIF in vitro [18].
• Moreover, differentiation-specific markers such as cytokeratin 10, involucrin, and filaggrin were shown to be expressed in an ordered succession [19].
• Most importantly, the analysis of ceramide subpopulations revealed that the total amount of ceramide 2 was elevated in keratin 10-deficient mice, whereas ceramides 1, 3, 4, and 5 were decreased among total stratum corneum lipids [20].

Regulatory relationships of Krt10

• After orthotopic transplantation to the floor of the mouth in athymic mice, cells containing dn TbetaR-II formed comparable numbers of primary tumours at the site of inoculation as controls but the tumours were less differentiated as demonstrated by the absence of keratin 10 immunostaining [21].

Other interactions of Krt10

• 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 [11].
• This intense staining for ODC occurred consistently in areas with decreased K1 and K10 expression, and, therefore, was associated with an altered pattern of differentiation [1].
• BAPTA also inhibited the expression of K1, K10 and loricrin mRNA [22].
• Although K10(-/-) mice show significant epidermal hyperproliferation, accompanied by an activation of the mitogen-activated protein kinase (MAPK) pathway, they formed no spontaneous tumors [23].
• In newborn mutant epidermis, K6 and K16 are found to be most abundant in the outermost epidermal cells, a distribution opposite to that of K1 and K10 [24].

Analytical, diagnostic and therapeutic context of Krt10

• Based on cell culture experiments and transgenic mouse studies, it has been proposed that K10 suppresses cell proliferation and tumor formation in the skin [2].
• Epitope mapping of monoclonal antibodies to keratin 10T enabled us to study its distribution relative to keratin 6, which is highly expressed in keratin 10 knockout mice, by double-immunogold electron microscopy [25].
• Immunoelectron microscopy using anti-S60 and another antibody to keratin 10 showed specific binding to cornified envelope associated filamentous structures [26].
• The effect of TPA on the separate expression of the maturation-associated keratins K1 and K10 was studied by immunohistochemistry in an unperturbed replicative keratinocyte population of hairless mice epidermis in relation to changes in the cell cycle time during regeneration [27].
• Site-directed mutagenesis identified two lysines (K10 and K197) of BKLF as the sumoylation sites [28].

References