Caspase digestion-resistant homozygous keratin 18 mutation protects mouse liver from apoptosis and injury

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Caspase Cleavage of Keratin 18 and Reorganization of Intermediate Filaments during Epithelial Cell Apoptosis

Keratins 8 (K8) and 18 (K18) are major components of intermediate filaments (IFs) of simple epithelial cells and tumors derived from such cells. Structural cell changes during apoptosis are mediated by proteases of the caspase family. During apoptosis, K18 IFs reorganize into granular structures enriched for K18 phosphorylated on serine 53. K18, but not K8, generates a proteolytic fragment duri...

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Epiplakin attenuates experimental mouse liver injury by chaperoning keratin reorganization

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Mutation of caspase-digestion sites in keratin 18 interferes with filament reorganization, and predisposes to hepatocyte necrosis and loss of membrane integrity.

Keratin 18 (K18 or KRT18) undergoes caspase-mediated cleavage during apoptosis, the significance of which is poorly understood. Here, we mutated the two caspase-cleavage sites (D238E and D397E) in K18 (K18-DE), followed by transgenic overexpression of the resulting mutant. We found that K18-DE mice develop extensive Fas-mediated liver damage compared to wild-type mice overexpressing K18 (K18-WT...

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ژورنال

عنوان ژورنال: Journal of Cell Science

سال: 2017

ISSN: 1477-9137,0021-9533

DOI: 10.1242/jcs.187492