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

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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

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14-3-3 Proteins
Keratins
Hepatocytes
Mitosis
Epithelium
Phosphorylation
Keratin-8
Keratin-18
Intermediate Filament Proteins
Liver Regeneration
Acinar Cells
Hepatectomy
Transgenic Mice
K-18 conjugate
Staining and Labeling
Peptides

All Science Journal Classification (ASJC) codes

  • General

Cite this

Ku, Nam On ; Michie, Sara ; Resurreccion, Evelyn Z. ; Broome, Rosemary L. ; Omary, M. Bishr. / Keratin binding to 14-3-3 proteins modulates keratin filaments and hepatocyte mitotic progression. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 7. pp. 4373-4378.
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Keratin binding to 14-3-3 proteins modulates keratin filaments and hepatocyte mitotic progression. / Ku, Nam On; Michie, Sara; Resurreccion, Evelyn Z.; Broome, Rosemary L.; Omary, M. Bishr.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 7, 02.04.2002, p. 4373-4378.

Research output: Contribution to journalArticle

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AU - Michie, Sara

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AB - 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.

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