Abstract
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.
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Abbreviations
- IL-1β:
-
interleukin-1beta
- ICE:
-
interleukin-1β converting enzyme
- PCR:
-
polymerase chain reaction
- PARP:
-
poly (ADP-ribose) polymerase
- BSA:
-
bovine serum albumin
- PBS:
-
phosphate-buffered saline
- HRP:
-
horseradish peroxidase
- SDS:
-
sodium dodecyl sulphate
- Ac-DEVD-CHO:
-
N-acetyl-Asp-Glu-Val-Asp aldehyde
- LD:
-
low density
- HD:
-
high density
- BCC:
-
basal cell carcinoma
- SCC:
-
squamous cell carcinoma
- BSA-FAF:
-
bovine serum albumin-fatty acid-free
- RLB:
-
reporter lysis buffer
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Acknowledgements
This work was supported by National Institutes of Health Grant AG14357 (to ES Alnemri), and CA81008 (to U Rodeck). SM Srinivasula is a special fellow of the Leukemia & Limphoma Society.
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Pistritto, G., Jost, M., Srinivasula, S. et al. Expression and transcriptional regulation of caspase-14 in simple and complex epithelia. Cell Death Differ 9, 995–1006 (2002). https://doi.org/10.1038/sj.cdd.4401061
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DOI: https://doi.org/10.1038/sj.cdd.4401061
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