Apoptosis generates stable fragments of human type I keratins

Nam-on Ku, Jian Liao, M. Bishr Omary

Research output: Contribution to journalArticle

193 Citations (Scopus)

Abstract

Type I and II keratins help maintain the structural integrity of epithelial cells. Since apoptosis involves progressive cell breakdown, we examined its effect on human keratin polypeptides 8, 18, and 19 (K8, K18, K19) that are expressed in simple-type epithelia as noncovalent type I (K18, K19) and type II (KS) heteropolymers. Apoptosis induces rapid hyperphosphorylation of most known K8/18 phosphorylation sites and delayed formation of K18 and K19 stable fragments. In contrast, K8 is resistant to proteolysis and remains associated with the K18 fragments. Transfection of phosphorylation/glycosylation-mutant K8 and K18 does not alter fragment formation. The protein domains of the keratin fragments were determined using epitope-defined antibodies, and microsequencing indicated that K18 cleavage occurs at a conserved caspase-specific aspartic acid. The fragments are found preferentially within the detergent-insoluble pool and can be generated, in a phosphorylation-independent manner, by incubating keratins with caspase-3 or with detergent lysates of apoptotic cells but not with lysates of nonapoptotic cells. Our results indicate that type I keratins are targets of apoptosis-activated caspases, which is likely a general feature of keratins in most if not all epithelial cells undergoing apoptosis. Keratin hyperphosphorylation occurs early but does not render the keratins better substrates of the downstream caspases.

Original languageEnglish
Pages (from-to)33197-33203
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number52
DOIs
Publication statusPublished - 1997 Dec 26

Fingerprint

Type I Keratin
Keratins
Apoptosis
Phosphorylation
Caspases
Detergents
Type II Keratin
Epithelial Cells
Proteolysis
Glycosylation
Structural integrity
Aspartic Acid
Caspase 3
Transfection
K-18 conjugate
Epitopes
Epithelium
Cells
Peptides
Antibodies

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ku, Nam-on ; Liao, Jian ; Omary, M. Bishr. / Apoptosis generates stable fragments of human type I keratins. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 52. pp. 33197-33203.
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Apoptosis generates stable fragments of human type I keratins. / Ku, Nam-on; Liao, Jian; Omary, M. Bishr.

In: Journal of Biological Chemistry, Vol. 272, No. 52, 26.12.1997, p. 33197-33203.

Research output: Contribution to journalArticle

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