Expression and transcriptional regulation of caspase-14 in simple and complex epithelia.
Caspase-14 is a recent addition to the caspase family of aspartate proteases involved in apoptotic processes. Human caspase-14 appears to be only weakly processed during apoptosis, and it does not cleave classical caspase substrates. Post partum, caspase-14 is prominently expressed by human keratinocytes and reportedly participates in terminal differentiation of complex epithelia. Here we provide evidence challenging the view that caspase-14 expression or processing is linked exclusively to terminal keratinocyte differentiation. We demonstrate that caspase-14 expression extended to multiple cell lines derived from simple epithelia of the breast, prostate, and stomach. In keratinocytes and breast epithelial cells, caspase-14 expression was upregulated in high-density cultures and during forced suspension culture. These effects were primarily due to transcriptional activation as indicated by reporter gene assays using a 2 kb caspase-14 promoter fragment. Importantly, caspase-14 was not cleaved during forced suspension culture of either cell type although this treatment induced caspase-dependent apoptosis (anoikis). Forced expression of caspase-14 in immortalized human keratinocytes had no effect on cell death in forced suspension nor was the transfected caspase-14 processed in this setting. In contrast to postconfluent and forced suspension culture, terminal differentiation of keratinocytes induced in vitro by Ca2+ treatment was not associated with increased caspase-14 expression or promoter activity. Our results indicate that (1) caspase-14 is expressed not only in complex but also simple epithelia; (2) cells derived from complex and simple epithelia upregulate caspase-14 expression in conditions of high cell density or lack of matrix interaction and; (3) in both cell types this phenomenon is due to transcriptional regulation.
Center for Apoptosis Research, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
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G
Pistritto
M
M
Jost
S M
SM
Srinivasula
R
R
Baffa
J-L
JL
Poyet
C
C
Kari
Y
Y
Lazebnik
U
U
Rodeck
E S
ES
Alnemri
D000918:Antibody Specificity / Q000276:immunology; D001940:Breast / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D053456:Caspase 14; D020169:Caspases / Q000235:genetics*; D002448:Cell Adhesion / Q000502:physiology; D002451:Cell Compartmentation / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000201:enzymology / Q000254:growth & development; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology*; D004848:Epithelium / Q000201:enzymology* / Q000254:growth & development; D005109:Extracellular Matrix / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D005809:Genes, Regulator / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics; D011467:Prostate / Q000166:cytology / Q000201:enzymology / Q000254:growth & development
C506446:CASP14 protein, human; D053456:Caspase 14; D020169:Caspases