Disease relevance of KRT15

• The expression of K15 mRNA and protein was also downregulated in two hyperproliferating situations, psoriasis and hypertrophic scars [1].
• The amino acid substitutions, K15Q and K15P, both yielded a non-N2-fixing phenotype when the genes coding for them were substituted into the Azotobacter vinelandii chromosome in place of the wild-type gene [2].
• Our study establishes K15 as one of the KSHV lytic genes that are inducing expression of multiple cytokines, which have been shown to play an important role in KSHV-associated pathogenesis [3].
• The Kaposi's sarcoma-associated herpesvirus (KSHV) (or human herpesvirus 8) open reading frame (ORF) K15 encodes a putative integral transmembrane protein in the same genomic location as latent membrane protein 2A of Epstein-Barr virus [4].
• K15 isolates from body cavity-based lymphoma (BCBL) cells exhibited a dramatic sequence variation and a complex splicing pattern [5].

High impact information on KRT15

• We show that a key factor is the presence of another keratin, K15, which was hitherto unappreciated as a basal cell component [6].
• Hybridization in situ with antisense riboprobes and/or synthetic oligonucleotides shows the presence of cytokeratin 15 mRNA in all layers of esophagus, whereas cytokeratin 4 mRNA tends to be suprabasally enriched, although to degrees varying in different regions [7].
• Basal layers of stratified epithelia express keratins K5, K14, and K15, which assemble into intermediate filament networks [8].
• Using cotransfection, gel mobility shifts, and DNase I footprinting, we have identified the regulators of K15 promoter activity and their binding sites [8].
• However, the thyroid hormone and IFN-gamma uniquely and potently activated the K15 promoter [8].

Chemical compound and disease context of KRT15

• However, the carboxy-terminal location of the candidate phosphotyrosine residues is more reminiscent of the Kaposi's sarcoma-associated herpesvirus K15 gene and provides potential evidence of an evolutionary transition from rhadinoviruses to lymphocryptoviruses [9].
• We used an interferon- gamma enzyme-linked immunospot assay with 56 specific peptides distributed on 6 HHV-8 proteins (glycoprotein [gp] B, gpH, gp35/37, latent nuclear antigen 1 [LANA-1], K12, and K15) to detect HHV-8-specific T cell responses.Results [10].

Biological context of KRT15

• The expression of keratin 15, the alternative basal cell keratin, was increased, suggesting upregulation or stabilization to compensate for the lack of keratin 14 [11].
• The genes for human cytokeratins 4 and 15 (KRT4 and 15) are assigned to the p11.2----q12 region of chromosome 12 (cytokeratin 4) and to the q21----q23 region of chromosome 17 (cytokeratin 15), respectively [12].
• Consistent with the in vitro data, we found a significant reduction of the K15 mRNA levels after skin injury, whereas K14 expression increased during the wound healing process [13].
• Cytokeratin 15 can be used to identify the limbal phenotype in normal and diseased ocular surfaces [14].
• Keratin 15 expression in stratified epithelia: downregulation in activated keratinocytes [1].

Anatomical context of KRT15

• These data demonstrate that K15 is excluded from the activated keratinocytes of the hyperthickened wound epidermis, possibly as a result of increased growth factor expression in injured skin [13].
• Immunostaining revealed the presence of K15 in all basal cells of the epidermis adjacent to the wound, but not in the hyperproliferative epithelium above the granulation tissue [13].
• The identified cDNA includes sequences of the keratin 15 (K15) gene which encodes a component of the cytoskeleton of basal cells in stratified epithelia [13].
• Although K15 in normal hair follicles was virtually absent from hair bulbs, it was expressed by a subset of keratinocytes in the outer root sheath [1].
• RESULTS: In human conjunctival epithelium, strong expression of K15 was observed in basal cells, whereas K19 was expressed in both basal and suprabasal layers (K15(bas)/K19(bas-sup)/K12(-)) [14].

Associations of KRT15 with chemical compounds

• METHODS AND RESULTS: Formalin-fixed paraffin-embedded tissues of 12 cases of primary EPD (three anal, nine vulvar) were studied immunohistochemically with antibodies to CK15 and CK19 [15].
• In K15 mice, [3H]thymidine incorporation of stage VIII tubule segments was decreased, suggesting that excess amounts of putrescine selectively inhibit meiotic DNA synthesis [16].
• While the CD8-K15 chimera was not capable of eliciting cellular signal transduction upon stimulation with an anti-CD8 antibody, it significantly inhibited B-cell receptor signaling, as evidenced by a suppression of tyrosine phosphorylation and intracellular calcium mobilization [5].
• K15 genotyping showed that 56% exhibited M form, of which 89% exhibited C3 K1 subtype and 44% exhibited P form [17].
• Results In the distant uninvolved skin the expression of beta1 integrin was decreased and keratin 15 expression was lost [18].

Other interactions of KRT15

• By comparison, K14 expression was found throughout the outer root sheath of hair follicles; however, when both K14 alleles were naturally ablated, the expression of K15 was also observed throughout the outer root sheath of the follicles [1].
• In organotypical cultures where differentiating keratinocytes expressed markers of activated phenotype, i.e., K6 and K16, expression of K15 was undetectable [1].
• Keratin 15 (K15) is a type I keratin without a defined type II partner whose expression in epidermal diseases has not been investigated [1].
• Using a specific CK15 antibody, 38% of TB showed a focal labeling and all BCC remained negative; 70% of TB and 22% of BCC expressed CK19 [19].
• Between K15 and K17 at least one additional, unidentified keratin gene is present [20].

Analytical, diagnostic and therapeutic context of KRT15

• Immunoelectron microscopy showed a loose network of keratin 5/keratin 15 protofilaments in the basal cells [11].
• Three of the former were identified by sequence analysis as stromelysin 1, a murine homolog of cytochrome P-450 F1 and cytokeratin 15 [21].
• We have further determined the downstream target genes of K15 signaling using DNA oligonucleotide microarrays [3].
• Northern blot analysis showed that K15 was weakly expressed in latently infected BCBL-1 cells, and the level of its expression was significantly induced by tetradecanoyl phorbol acetate stimulation [5].
• Molecular epidemiology of human herpesvirus 8 in africa: both B and A5 K1 genotypes, as well as the M and P genotypes of K14.1/K15 loci, are frequent and widespread [22].

References