Human elastase 1: Evidence for expression in the skin and the identification of a frequent frameshift polymorphism

Citation
U. Talas et al., Human elastase 1: Evidence for expression in the skin and the identification of a frequent frameshift polymorphism, J INVES DER, 114(1), 2000, pp. 165-170
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Dermatology,"da verificare
Journal title
JOURNAL OF INVESTIGATIVE DERMATOLOGY
ISSN journal
0022-202X → ACNP
Volume
114
Issue
1
Year of publication
2000
Pages
165 - 170
Database
ISI
SICI code
0022-202X(200001)114:1<165:HE1EFE>2.0.ZU;2-G
Abstract
Human pancreatic elastase 1 is a serine protease which maps to the chromoso mal region 12q13 close to a locus for an autosomal dominant skin disease, d iffuse nonepidermolytic palmoplantar keratoderma, and was investigated as a possible candidate gene for this disorder. Expression of two elastase inhi bitors, elafin and SLPI, has been related to several hyperproliferative ski n conditions. elastase 1 is functionally silent in the human pancreas but e lastase 1 expression at the mRNA level was detected in human cultured prima ry keratinocytes. Antibody staining localized the protein to the basal cell layer of the human epidermis at a number of sites including the palmoplant a. Sequencing of genomic DNA from individuals with/without the keratoderma revealed a sequence variant, which would result in a premature truncation o f the protein. This sequence variant, however, did not segregate with the s kin disease and, indeed, was found to occur at a relatively high frequency in the population. Individuals homozygous for the variant do not have any o bvious skin abnormalities. Based on the analysis of the secondary structure of the translated putative protein, the truncation is unlikely to result i n knock-out of the elastase, but may cause destabilization of the enzyme-in hibitor complex.