The mouse S100A15 ortholog parallels genomic organization, structure, gene expression, and protein-processing pattern of the human S100A7/A15 subfamily during epidermal maturation.
The calcium-binding proteins of the human S100A7/A15 (hS100A7/A15) subfamily are differentially expressed in normal and pathological epidermis. The hS100A7 (psoriasin) and S100A15 reside in a chromosomal cluster of highly similar paralogs. To exploit the power of mouse models for determining functions of gene products, the corresponding S100A7/A15 ortholog was cloned and examined in murine skin. The single mouse S100A15 (mS100A15) gene encodes a protein of 104 amino acids with a predicted molecular weight of 12,870 Da and two EF-hand calcium binding sites. Using gene-specific primers and specific antibodies, expression of mS100A15 in both skin and isolated keratinocytes is confined to differentiating granular and cornified epidermal cells. Immunoblotting of epidermal extracts revealed a series of high molecular weight bands that are also recognized by an antibody for transglutaminase-mediated protein crosslinks. mS100A15 expression is upregulated in cultured keratinocytes induced to differentiate by calcium or phorbol esters. Maximal induction occurs concordantly with expression of late differentiation markers. Induction is enhanced in keratinocytes overexpressing protein kinase Calpha and is dependent on activator protein-1 transcription factors. The regulation, expression pattern and crosslinking of mS100A15 are consistent with the characteristics of the human orthologs, providing a valid surrogate model to study changes in these proteins associated with cutaneous pathologies.
Wolf
Ronald
R
Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA.
Voscopoulos
Christopher J
CJ
FitzGerald
Peter C
PC
Goldsmith
Paul
P
Cataisson
Christophe
C
Gunsior
Michele
M
Walz
Markus
M
Ruzicka
Thomas
T
Yuspa
Stuart H
SH
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002874:Chromosome Mapping; D000078404:Epidermal Cells; D004817:Epidermis / Q000737:chemistry / Q000254:growth & development* / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000737:chemistry / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D010703:Phorbol Esters / Q000494:pharmacology; D051571:Protein Kinase C-alpha / Q000502:physiology; D011499:Protein Processing, Post-Translational; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D012871:Skin Diseases / Q000503:physiopathology; D012878:Skin Neoplasms / Q000235:genetics
D000596:Amino Acids; D002135:Calcium-Binding Proteins; D010703:Phorbol Esters; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C512053:S100A15 protein, mouse; C089242:S100A7 protein, human; C510475:S100A7A protein, human; D051571:Protein Kinase C-alpha; D002118:Calcium