Keratin Binding to 14-3-3 Proteins Modulates Keratin Filaments and Hepatocyte Mitotic Progression

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 99; no. 7; pp. 4373 - 4378
• Main Authors: Ku, Nam-On, Michie, Sara, Resurrecdon, Evelyn Z., Broome, Rosemary L., Omary, M. Bishr
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 02.04.2002; National Acad Sciences; The National Academy of Sciences
• Subjects: 14-3-3 protein; 14-3-3 Proteins; Acinar cells; Animals; Biological Sciences; Cellular biology; Hepatectomy; Hepatocytes; Hepatocytes - physiology; Keratins; Keratins - chemistry; Keratins - genetics; Keratins - physiology; Laboratory staining techniques; Liver; Mice; Mice, Transgenic; Mitosis; Mutation; Peptides; Phosphorylation; Proteins; Transgenes; Transgenic animals; Tyrosine 3-Monooxygenase - analysis; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.072624299

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.