Keratin binding to 14-3-3 proteins modulates keratin filaments and hepatocyte mitotic progression

Nam On Ku, Sara Michie, Evelyn Z. Resurreccion, Rosemary L. Broome, M. Bishr Omary

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Keratin polypeptides 8 and 18 (K8/18) are the major intermediate filament proteins of simple-type epithelia. K18 Ser-33 phosphorylation regulates its binding to 14-3-3 proteins during mitosis. We studied the significance of keratin binding to 14-3-3 in transgenic mice that overexpress wild-type or Ser-33→Ala (S33A) K18. In S33A but not wild-type K18-overexpressing mice, pancreatic acinar cell keratin filaments retracted from the basal nuclear region and became apically concentrated. In contrast, K18 S33A had a minimal effect on hepatocyte keratin filament organization. Partial hepatectomy of K18-S33A-overexpressing mice did not affect liver regeneration but caused limited mitotic arrest, accumulation of abnormal mitotic figures, dramatic fragmentation of hepatocyte keratin filaments, with retention of a speckled 14-3-3ζ mitotic cell nuclear-staining pattern that usually becomes diffuse during mitosis. Hence, K18 Ser-33 phosphorylation regulates keratin filament organization in simple-type epithelia in vivo. Keratin binding to 14-3-3 may partially modulate hepatocyte mitotic progression, in association with nuclear redistribution of 14-3-3 proteins during mitosis.

Original languageEnglish
Pages (from-to)4373-4378
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number7
DOIs
Publication statusPublished - 2002 Apr 2

All Science Journal Classification (ASJC) codes

  • General

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