Epidermal differentiation does not involve the pro-apoptotic executioner caspases, but is associated with caspase-14 induction and processing
Open accessAbstract
The epidermis is a stratified squamous epithelium in which keratinocytes progressively undergo terminal differentiation towards the skin surface leading to programmed cell death. In this respect we studied the role of caspases. Here, we show that caspase-14 synthesis in the skin is restricted to differentiating keratinocytes and that caspase-14 processing is associated with terminal epidermal differentiation. The pro-apoptotic executioner caspases-3, -6, and -7 are not activated during epidermal differentiation. Caspase-14 does not participate in apoptotic pathways elicited by treatment of differentiated keratinocytes with various death-inducing stimuli, in contrast to caspase-3. In addition, we show that non-cornifying oral keratinocyte epithelium does not express caspase-14 and that the parakeratotic regions of psoriatic skin lesions contain very low levels of caspase-14 as compared to normal stratum corneum. These observations strongly suggest that caspase-14 is involved in the keratinocyte terminal differentiation program leading to normal skin cornification, while the executioner caspases are not implicated. Cell Death and Differentiation (2000) 7, 1218 - 1224
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Cornification critically relies on CASP14 and multiple transglutaminase isoforms and has long been considered a form of PCD.
“The latter process, which is commonly known as cornification (or keratinization) and critically relies on CASP14 [1026, 1027] and multiple isoforms of transglutaminase [1025, 1028, 1029], has long been considered as a form of PCD [1025, 1030].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [1026]
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- Authors
- Lippens, S., Kockx, M., Knaapen, M., Mortier, L., Polakowska, R., Verheyen, A., Garmyn, M., Zwijsen, A., Formstecher, P., Huylebroeck, D., Vandenabeele, P., & Declercq, W.
- Affiliations
- Vlaams Instituut voor Biotechnologie (BE)
- ZNA Middelheim Hospital (BE)
- Inserm (FR)
- KU Leuven (BE)
- Corresponding author
- Vandenabeele, P
- Venue
- Cell Death & Differentiation
- Published
- 2000-12
- Volume
- 7
- Issue
- 12
- Pages
- 1218-1224
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- OpenAlex
- W1984028519
- Cited by
- 245
- References
- 39
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 9 · 2023: 9 · 2022: 5 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 9 · 2017: 5 · 2016: 5 · 2015: 12 · 2014: 10 · 2013: 14 · 2012: 8
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Death and Differentiation (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion, other-oa)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Funders
- Fonds Wetenschappelijk Onderzoek
- Vlaamse regering
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Calpain Protease Function and Regulation
- Keywords
- CASP14, epidermal differentiation, keratinocyte terminal differentiation, keratinization, executioner caspases, caspase-3, caspase-6, caspase-7, apoptosis, psoriasis, oral keratinocytes, parakeratosis, stratum corneum
- MeSH terms
- Epidermal Cells, Animals, Cell Differentiation, Cells, Cultured, Epidermis, Fetus, Humans, Immunohistochemistry, Mice, Inbred C57BL, Psoriasis, Keratinocytes, Apoptosis, Caspases, Mice, Caspase 3, Caspase 6, Caspase 7, Caspase 14
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