Cloning and characterization of multiple human genes and cDNAs encoding highly related type II keratin 6 isoforms

K. Takahashi, R. D. Paladini, P. A. Coulombe

Research output: Contribution to journalArticle

Abstract

The human type II keratin 6 (K6; 56 kDa) is expressed in a heterogeneous array of epithelial tissues under normal conditions, but is better known for its strong induction in stratified epithelia that feature an enhanced cell proliferation rate or abnormal differentiation. Previous work has established the existence of two functional genes encoding K6 protein isoforms in the human genome, although only a partial cDNA clone is available for K6a, the dominant human K6 isoform in skin epithelial tissues (Tyner, A., and Fuchs, E. (1986) J. Cell Biol. 103, 1945-1955). We screened human genomic and skin cDNA libraries with probes derived from the K6b gene, and isolated clones containing the full-length gene and cDNA predicted to encode K6a. A thorough characterization of a large number of genomic (57) as well as cDNA (64) clones further revealed the existence of as many as six different human K6 protein isoforms that are highly related at the gene structure, nucleotide sequence, and predicted amino acid sequence levels. Based on the information accumulated to date we propose an evolutionary model in which the multiplicity of human K6 genes is explained by successive gene duplication events. We further demonstrate that K6a is clearly the dominant K6 isoform in skin tissue samples and cultured epithelial cell lines and that the various isoforms are differentially regulated within and between epithelial tissue types. Our findings have direct implications for an understanding of the regulation and function of K6 during hyperproliferation in stratified epithelia and the search for disease-causing mutations in K6 sequences in the human population.

Original languageEnglish (US)
Pages (from-to)18581-18592
Number of pages12
JournalJournal of Biological Chemistry
Volume270
Issue number31
DOIs
StatePublished - 1995

Fingerprint

Type II Keratin
Keratin-6
Cloning
Organism Cloning
Protein Isoforms
Complementary DNA
Genes
Epithelium
Tissue
Skin
Clone Cells
Gene encoding
Gene Duplication
Cell proliferation
Human Genome
Gene Library
Amino Acid Sequence
Cultured Cells
Nucleotides
Epithelial Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cloning and characterization of multiple human genes and cDNAs encoding highly related type II keratin 6 isoforms. / Takahashi, K.; Paladini, R. D.; Coulombe, P. A.

In: Journal of Biological Chemistry, Vol. 270, No. 31, 1995, p. 18581-18592.

Research output: Contribution to journalArticle

Takahashi, K. ; Paladini, R. D. ; Coulombe, P. A. / Cloning and characterization of multiple human genes and cDNAs encoding highly related type II keratin 6 isoforms. In: Journal of Biological Chemistry. 1995 ; Vol. 270, No. 31. pp. 18581-18592.
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