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The cornified envelope: a model of cell death in the skin
Abstract
The epidermis functions as a barrier against the environment by means of several layers of terminally differentiated, dead keratinocytes - the cornified layer, which forms the endpoint of epidermal differentiation and death. The cornified envelope replaces the plasma membrane of differentiating keratinocytes and consists of keratins that are enclosed within an insoluble amalgam of proteins, which are crosslinked by transglutaminases and surrounded by a lipid envelope. New insights into the molecular mechanisms and the physiological endpoints of cornification are increasing our understanding of the pathological defects of this unique form of programmed cell death, which is associated with barrier malfunctions and ichthyosis.
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“A portion of EO ceramides are converted into protein-bound hydroxy (P-O) ceramides (Fig. 1B), which are connected to cross-linked proteins constituting the cornified envelope, a structure located beneath the surface of corneocytes (20)(21)(22).”
From Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS/MS (2020) · cites this paper as [20]
In the citing paper
“Unlike plasma membranes in general, which are constituted by a lipid bilayer, corneocytes are covered by a lipid monolayer mainly composed of P-O ceramides (20), which are presumed to link corneocytes to the lipid lamellae.”
From Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS/MS (2020) · cites this paper as [20]
In the citing paper
“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 [1025]
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Metadata
- Authors
- Candi, E., Schmidt, R., & Melino, G.
- Affiliations
- University of Rome Tor Vergata (IT)
- L'Oréal (France) (FR)
- Corresponding author
- Melino, Gerry
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2005-04
- Volume
- 6
- Issue
- 4
- Pages
- 328-340
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- OpenAlex
- W2005630031
- Cited by
- 1,776
- References
- 216
- Citations by year
- 2026: 58 · 2025: 68 · 2024: 85 · 2023: 99 · 2022: 77 · 2021: 96 · 2020: 107 · 2019: 74 · 2018: 97 · 2017: 86 · 2016: 94 · 2015: 83 · 2014: 95 · 2013: 110 · 2012: 98
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Funders
- National Institutes of Health
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Dermatology › Genetic and rare skin diseases.
- Keywords
- cornified envelope, keratinization, keratinocytes, epidermal differentiation, programmed cell death, keratin, transglutaminase cross-linking, skin barrier, ichthyosis, skin barrier dysfunction
- MeSH terms
- Epidermal Cells, Filaggrin Proteins, Animals, Cell Adhesion, Cell Differentiation, Epidermis, Humans, Intermediate Filament Proteins, Membrane Proteins, Protein Precursors, Transglutaminases, Substrate Specificity, Apoptosis, Genetic Diseases, Inborn
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