Caspase activation in the terminal differentiation of human epidermal keratinocytes.
The epidermis is a multilayered squamous epithelium in which dividing basal cells withdraw from the cell cycle and progressively differentiate as they are displaced toward the skin surface. Eventually, the cells lose their nucleus and other organelles to become flattened squames, which are finally shed from the surface as bags of cross-linked keratin filaments enclosed in a cornified envelope [1]. Although keratinocytes can undergo apoptosis when stimulated by a variety of agents [2], it is not known whether their normal differentiation programme uses any components of the apoptotic biochemical machinery to produce the cornified cell. Differentiating keratinocytes have been reported to share some features with apoptotic cells, such as DNA fragmentation, but these features have not been seen consistently [3]. Apoptosis involves an intracellular proteolytic cascade, mainly mediated by members of the caspase family of cysteine proteases, which cleave one another and various key intracellular target proteins to kill the cell neatly and quickly [4]. Here, we show for the first time that caspases are activated during normal human keratinocyte differentiation and that this activation is apparently required for the normal loss of the nucleus.
Weil
M
M
Medical Research Council Laboratory for Molecular Cell Biology, Department of Biology, University College London, London WC1E 6BT, UK.
Raff
M C
MC
Braga
V M
VM
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D015153:Blotting, Western; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000032:analysis / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology*; D000091344:Filaggrin Proteins; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000032:analysis / Q000187:drug effects; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008297:Male
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C103192:butyloxycarbonyl-O-methyl-aspartyl-fluoromethyl ketone; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases