Epidermal differentiation does not involve the pro-apoptotic executioner caspases, but is associated with caspase-14 induction and processing.
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
Lippens
S
S
Molecular Signaling and Cell Death Unit, Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and Ghent University, K.L. Ledeganckstraat 35, B-9000 Ghent, Belgium.
Kockx
M
M
Knaapen
M
M
Mortier
L
L
Polakowska
R
R
Verheyen
A
A
Garmyn
M
M
Zwijsen
A
A
Formstecher
P
P
Huylebroeck
D
D
Vandenabeele
P
P
Declercq
W
W
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053456:Caspase 14; D053148:Caspase 3; D053178:Caspase 6; D053179:Caspase 7; D020169:Caspases / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000201:enzymology* / Q000502:physiology*; D005333:Fetus; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D011565:Psoriasis / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology
C506446:CASP14 protein, human; C505407:CASP3 protein, human; C505514:CASP6 protein, human; C505520:CASP7 protein, human; C506449:Casp14 protein, mouse; C505409:Casp3 protein, mouse; C505516:Casp6 protein, mouse; C505524:Casp7 protein, mouse; D053456:Caspase 14; D053148:Caspase 3; D053178:Caspase 6; D053179:Caspase 7; D020169:Caspases