Keratin binding to 14-3-3 proteins modulates keratin filaments and hepatocyte mitotic progression.
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.
Ku
Nam-On
NO
Department of Medicine, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Avenue, 154J, Palo Alto, CA 94304, USA.
Michie
Sara
S
Resurreccion
Evelyn Z
EZ
Broome
Rosemary L
RL
Omary
M Bishr
MB
D048948:14-3-3 Proteins; D000818:Animals; D006498:Hepatectomy; D022781:Hepatocytes / Q000502:physiology*; D007633:Keratins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008938:Mitosis; D009154:Mutation; D010766:Phosphorylation; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000378:metabolism*
D048948:14-3-3 Proteins; D007633:Keratins; D014446:Tyrosine 3-Monooxygenase