Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

Herro, R. et al. LIGHT–HVEM signaling in keratinocytes controls development of dermatitis. J. Exp. Med. 215, 415–422 (2018). In a 28-year-old man (IWC100) with ichthyosis with confetti (IWC; 609165), Lim et al. (2016) identified heterozygosity for a de novo 1-bp deletion (c.1373delG) at the last base of exon 6 of the KRT10 gene, causing a frameshift that replaced the endogenous glycine-rich tail domain of keratin-10 with an alanine-rich motif that extended the C terminus by 19 additional amino acids. Immunolocalization in affected skin showed an overall reduction in suprabasal K10 staining, with evidence of filament network collapse and focal aggregates within the nucleus; these findings were not seen in revertant or normal control skin. Costaining with a nucleolar marker revealed K10 aggregates within the nucleolus. Immunolocalization of the KRT10 binding partner KRT1 (139350) also demonstrated nuclear mislocalization. Laser-capture microdissection of 3 white spots revealed that each revertant spot harbored copy-neutral loss of heterozygosity in the proximal q arm of chromosome 17 extending to the telomere, consistent with reversion via mitotic recombination. For all 3 revertant spots, the region of crossover was estimated to fall between SNPs rs6505079 and rs8078229. Liu, Y.-L. et al. Amelioration of amyloid-β-induced deficits by DcR3 in an Alzheimer’s disease model. Mol. Neurodegener. 12, 30 (2017). Truong, A. B. & Khavari, P. A. Control of keratinocyte proliferation and differentiation by p63. Cell Cycle 6, 295–299 (2007).

Permitted

Identification of the genetic locus for keratosis palmaris et plantaris on chromosome 17 near the RARA and keratin type I genes.

Renz et al. (2019) noted that the genodermatosis IWC is caused by dominant-negative variants that result in aberrant KRT10 proteins that localize to the nucleus rather than the cytoplasm. The mislocalization is associated with a C terminus that is altered from a polyglycine tail to either a polyarginine or polyalanine tail. Renz et al. (2019) demonstrated that only K10 with an arginine-rich C terminus (K10arg) translocates to the nucleus, whereas wildtype K10, K10ala, and truncated K10 remain in the cytoplasm. The authors also showed that the presence of K10arg enables cotranslocation of non-K10arg proteins into the nucleus. They concluded that arginine-rich K10 tails are responsible for the pathogenic nuclear localization of K10 in patients with IWC. Superficial epidermolytic ichthyosis (ichthyosis bullosa of Siemens) — mutations in keratin gene KRT2 Yang JM, Nam K, Kim SW, etal. (1999). "Arginine in the beginning of the 1A rod domain of the keratin 10 gene is the hot spot for the mutation in epidermolytic hyperkeratosis". J. Dermatol. Sci. 19 (2): 126–33. doi: 10.1016/S0923-1811(98)00055-3. PMID 10098704.Figure 6 Decreased Akt and PKCζ activities in bK5hK10 transgenic mouse epidermis. Immunofluorescence analysis of the Akt expression in non-transgenic ( A) and homozygous transgenic ( A′) newborn mouse epidermis, showing similar staining throughout the entire epidermis in both cases. B and B′, the same field as in A and A′, showing that the expression of phosphorylated (active) Akt is constrained to the basal layer in non-transgenic mice ( B) and that staining is severely reduced in homozygous transgenic epidermis ( B′). C and C′, 4′,6-diamidino-2-phenylindole counterstaining of the sections. D, Western blot of whole skin extracts from the quoted genotypes demonstrating the decrease in phosphorylated Akt content in homozygous mice epidermis. E, kinase assays of the immunoprecipitated endogenous Akt ( upper panel) and PKCζ ( middle panel) demonstrating the inhibition of both kinase activities in homozygous, and to a lesser extent in heterozygous, transgenic bK5hK10 epidermis. The lower panel shows the Western blot of the immunoprecipitated PKCζ, demonstrating that this enzyme is expressed to a similar level in all the genotypes. Bar in C = 10 μm. Dashed lines in A and A′ denote the dermal-epidermal junction. Erratico S et al. Effective high-throughput isolation of enriched platelets and circulating pro-angiogenic cells to accelerate skin-wound healing. Cell Mol Life Sci 79:259 (2022). Status: REVIEWED Source sequence(s) AC090283 Consensus CDS CCDS92302.1 UniProtKB/TrEMBL A0A1B0GVI3 Related ENSP00000490524.2, ENST00000635956.2 Conserved Domains (1) summary pfam00038

Equal amounts of soluble protein were used for measurement of total kinase activity with a PKC kinase activity kit (ENZO Life Sciences, Farmingdale, NY, USA) according to the manufacturer’s instructions. For the PKCα and PKCδ kinase assays, immunoprecipitation followed by an in vitro kinase assay was carried out as described previously 24. An anti-PKC antibody was applied, and MBP was used as the substrate. Statistical analysis siRNA experiments were performed by using siRNAs targeting human DcR3, PKCα, and PKCδ and a nontargeting siRNA as the control (Thermo Fisher Scientific, Lafayette, CO, USA). NHEKs at approximately 50% confluence were transfected with 100 nM siRNA with DharmaFECT Transfection Reagent following the manufacturer’s instructions. Cells were harvested at the indicated time points. Immunoblotting Lessin SR, Huebner K, Isobe M, Croce CM, Steinert PM (Jan 1989). "Chromosomal mapping of human keratin genes: evidence of non-linkage". J Invest Dermatol. 91 (6): 572–8. doi: 10.1111/1523-1747.ep12477087. PMID 2461420.Schweizer J, Bowden PE, Coulombe PA, Langbein L, Lane EB, Magin TM, Maltais L, Omary MB, Parry DA, Rogers MA, Wright MW (Jul 2006). "New consensus nomenclature for mammalian keratins". J Cell Biol. 174 (2): 169–74. doi: 10.1083/jcb.200603161. PMC 2064177. PMID 16831889.