Transient activation of cyclin B/Cdc2 during terminal differentiation of lens fiber cells.
Previous work has shown that postmitotic, differentiating fiber cells of the embryonic chicken lens express cyclin B and Cdc2. The present study explores the possible physiological role of these proteins in lens differentiation by examining the developmental regulation of cyclin B/Cdc2 expression and activity in lens fiber cells of embryonic and newborn rats. Cyclin B mRNA and protein were detected not only in the lens epithelium, which contains proliferating cells, but also in postmitotic, differentiating fiber cells. In contrast, cyclin A mRNA and protein were detected only in epithelial cells. Immunoprecipitation with cyclin B antibody coprecipitated Cdc2 from both epithelial and fiber cell extracts. Immunoprecipitates of cyclin B from both epithelial cells and fiber cells showed H1 kinase activity when assayed in vitro, but the developmental pattern of cyclin B-associated kinase activity in these two lens fractions was markedly different. In the epithelium, H1 kinase activity decreased gradually with developmental age in parallel with the decrease in epithelial cell proliferation, whereas, in the fiber cells, kinase activity peaked sharply at embryonic day 18 (E18) and E19. Microscopic examination of rat lenses indicated that peak cyclin B/Cdc2 activity was correlated with changes in chromatin structure and nuclear envelope breakdown in the terminally differentiating primary lens fiber cells. These findings suggest that cyclin B/Cdc2 activity may play an active role in nuclear changes leading to primary fiber cell denucleation.
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National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Gao
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Vrensen
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Zelenka
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D000818:Animals; D000831:Animals, Newborn; D016203:CDC2 Protein Kinase / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002457:Cell Extracts; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D002843:Chromatin; D019925:Cyclin A / Q000032:analysis / Q000235:genetics; D019926:Cyclin B / Q000032:analysis* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006367:HeLa Cells; D006801:Humans; D007908:Lens, Crystalline / Q000737:chemistry / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D006656:Protamine Kinase / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D002457:Cell Extracts; D002843:Chromatin; D019925:Cyclin A; D019926:Cyclin B; D012333:RNA, Messenger; D006656:Protamine Kinase; D016203:CDC2 Protein Kinase