Disease relevance of Krt16

• In hypertrophic scars the mRNA distribution corroborated the abnormal K16 protein distribution [1].
• Analysis of the lesional keratins of psoriasis patients showed that etretinate caused a reduction in keratin 16 and an increase in the keratin 14:keratin 16 ratio, although the magnitude of these changes and their correlation with clinical improvement was variable [2].
• The availability of K16 in a purified recombinant form will allow us to study how its properties may relate to its function during wound healing and in skin diseases [3].
• The acetylation pattern of histone H4 in mouse lymphosarcoma cells induced by TSA was established in which acetylation initially occurred at K16 followed by K12 and then K8 and/or K5 [4].

High impact information on Krt16

• Absence of a hair phenotype correlates with a genetic strain-dependent compensation by related keratins, including K16 [5].
• The inability of K16 to form urea-stable tetramers in vitro correlates with an increase in its turnover rate in vivo [6].
• While a structural function has been clearly defined for K14, we have proposed that a function of K16 may be to play a role in the process of keratinocyte activation that occurs after acute injury to stratified epithelia [7].
• In fact, tyrosine phosphorylation of the EGF receptor is increased in the newborn skin of K16 transgenic mice [8].
• 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 [9].

Biological context of Krt16

• The functional diversity of epidermal keratins revealed by the partial rescue of the keratin 14 null phenotype by keratin 16 [7].
• Rather, these data implicate the tail domain of K16 as the more likely protein domain that determines the unique functions [10].
• We therefore used the skin of heterozygous and homozygous mice to create a cDNA library, and we report here the successful cloning and sequencing of mouse K16 [10].
• These remarkable changes were accompanied by the induction of c-Myc, cyclin D1, 14-3-3sigma and of wound healing keratins K6 and K16 [11].
• In this study, we analyzed the distribution of mouse type I keratin 16 during skin morphogenesis, in the adult hair cycle, and in challenged epidermis [12].

Anatomical context of Krt16

• In control animals, K6 and K16 were found only in the hair follicles [13].
• Keratin 16 expression defines a subset of epithelial cells during skin morphogenesis and the hair cycle [12].
• These additional cytokeratins consisted of cytokeratin 16 in all six cell lines and cytokeratins 4, 13, and 16 in one cell line [14].
• To examine the properties of K16 in its natural cellular context, we introduced a wild-type human K16 gene into the germ line of transgenic mice [15].

Associations of Krt16 with chemical compounds

• The BrdUrd-labelled cell cohort was followed for 96 h after TPA-treatment by two-colour immunofluorescence staining with antibodies to BrdUrd, keratin K6 and K16 [13].
• Hyperplasia-inducing agents (salicylic acid, croton oil) caused an increase in keratins K6, K16, and K17, but they did not effect filaggrin or alter proteolysis of stratum corneum keratins [16].
• In both types of SPPK upregulation of K16 was pronounced and involucrin labelling was abnormal [17].

Other interactions of Krt16

• Our results suggest that the expression of K6 and K16 is less restricted by cellular replication than the normally occurring K1 and K10 keratins [13].
• Exposure of cultures to a variety of different retinoids produced both dose-dependent decreases in keratin 16 with consequent increases in the keratin 14: keratin 16 ratio, and a decrease in envelope formation [2].
• A conserved aspect of this response is a rapid switch in gene expression whereby the type II keratin 6 (K6) and type I keratins 16 and 17 (K16, K17) are induced in epithelial cells at the wound edge [18].

Analytical, diagnostic and therapeutic context of Krt16

• K16 mRNA was localized by in situ hybridization using a highly specific cRNA probe [1].
• Keratin 6, keratin 16, and keratin 17, which are known to be upregulated during keratinocyte activation and in hyperproliferative epidermis, were highly expressed in cultured skin substitutes in vitro [19].
• By real-time PCR, TH replete cell expression of K6a, K16, and K17 was greater than in deficient cells: 18- (P < 0.001), 10- (P < 0.001), and 4-fold (P < 0.005), respectively [20].
• By RT-PCR, keratin 6a (K6a) and 16 (K16) gene expression in TH replete cells was 3.8- (P < 0.005) and 1.9-fold (P < 0.05) greater, respectively, than expression in TH-deficient cells [20].

References