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

First Author  Ku NO Year  2002
Journal  Proc Natl Acad Sci U S A Volume  99
Issue  7 Pages  4373-8
PubMed ID  11917136 Mgi Jnum  J:135384
Mgi Id  MGI:3793539 Doi  10.1073/pnas.072624299
Citation  Ku NO, et al. (2002) Keratin binding to 14-3-3 proteins modulates keratin filaments and hepatocyte mitotic progression. Proc Natl Acad Sci U S A 99(7):4373-8
abstractText  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 14-3-3zeta 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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