| http://purl.uniprot.org/citations/31220272 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31220272 | http://www.w3.org/2000/01/rdf-schema#comment | "The type I intermediate filament keratin 16 (KRT16 gene; K16 protein) is constitutively expressed in ectoderm-derived appendages and in palmar/plantar epidermis and is robustly induced when the epidermis experiences chemical, mechanical or environmental stress. Missense mutations at the KRT16 locus can cause pachyonychia congenita (PC, OMIM:167200) or focal non-epidermolytic palmoplantar keratoderma (FNEPPK, OMIM:613000), which each entail painful calluses on palmar and plantar skin. Krt16-null mice develop footpad lesions that mimic PC-associated PPK, providing an opportunity to decipher its pathophysiology, and develop therapies. We report on insight gained from a genome-wide analysis of gene expression in PPK-like lesions of Krt16-null mice. Comparison of this data set with publicly available microarray data of PPK lesions from individuals with PC revealed significant synergies in gene expression profiles. Keratin 9 (Krt9/K9), the most robustly expressed gene in differentiating volar keratinocytes, is markedly downregulated in Krt16-null paw skin, well-ahead of lesion onset, and is paralleled by pleiotropic defects in terminal differentiation. Effective prevention of PPK-like lesions in Krt16-null paw skin (via topical delivery of the Nrf2 inducer sulforaphane) involves the stimulation of Krt9 expression. These findings highlight a role for defective terminal differentiation and loss of Krt9/K9 expression as additional drivers of PC-associated PPK and highlight restoration of KRT9 expression as a worthy target for therapy. Further, we report on the novel observation that keratin 16 can localize to the nucleus of epithelial cells, implying a potential nuclear function that may be relevant to PC and FNEPPK."xsd:string |
| http://purl.uniprot.org/citations/31220272 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/ddz050"xsd:string |
| http://purl.uniprot.org/citations/31220272 | http://purl.uniprot.org/core/author | "Coulombe P.A."xsd:string |
| http://purl.uniprot.org/citations/31220272 | http://purl.uniprot.org/core/author | "Ma J."xsd:string |
| http://purl.uniprot.org/citations/31220272 | http://purl.uniprot.org/core/author | "Poll B.G."xsd:string |
| http://purl.uniprot.org/citations/31220272 | http://purl.uniprot.org/core/author | "Zieman A.G."xsd:string |
| http://purl.uniprot.org/citations/31220272 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/31220272 | http://purl.uniprot.org/core/name | "Hum Mol Genet"xsd:string |
| http://purl.uniprot.org/citations/31220272 | http://purl.uniprot.org/core/pages | "2255-2270"xsd:string |
| http://purl.uniprot.org/citations/31220272 | http://purl.uniprot.org/core/title | "Altered keratinocyte differentiation is an early driver of keratin mutation-based palmoplantar keratoderma."xsd:string |
| http://purl.uniprot.org/citations/31220272 | http://purl.uniprot.org/core/volume | "28"xsd:string |
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