Polyploidization and Functional Maturation Are Two Distinct Processes During Megakaryocytic Differentiation: Involvement of Cyclin-Dependent Kinase Inhibitor p21 in Polyploidization
| Autor: | Yusuke Furukawa, Satsuki Iwase, Mitsuru Nakamura, Yasusada Miura, Masatoshi Kitagawa, Jiro Kikuchi, Seiichi Kitagawa, Yasuhito Terui, Norio Komatsu |
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| Rok vydání: | 1997 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Cellular differentiation Immunology HL-60 Cells Biology Biochemistry Polyploidy chemistry.chemical_compound Cyclin-dependent kinase Cyclins Humans Mitosis Phorbol 12 13-Dibutyrate Cyclin-dependent kinase 1 Nocodazole Cell Differentiation Cell Biology Hematology Molecular biology Cell biology Haematopoiesis Licensing factor chemistry Carcinogens biology.protein Megakaryocytes CDC2 Protein Kinase |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v89.11.3980 |
| Popis: | The mechanism of megakaryocytic differentiation was investigated using human megakaryocytic leukemia cell line UT-7. Polyploidization of UT-7 cells was induced by the microtubule-depolymerizing agent, nocodazole, and 12-O-tetradecanoylphorbol-13-acetate (TPA), but the effect was much more striking with nocodazole. By contrast, induction of cytoplasmic maturation, as judged by β-thromboglobulin production and platelet factor 4 expression, was more prominent in TPA-treated cells than in nocodazole-treated cells. Nocodazole and TPA could act synergistically to increase ploidy and to enhance the expression of mature phenotypes. Human thrombopoietin induced functional maturation but not polyploidization in UT-7 cells and also acts synergistically with nocodazole. Cyclin-dependent kinase inhibitor p21 was upregulated at the early stage of megakaryocytic differentiation, and overexpression of p21 resulted in an increase in ploidy of UT-7 cells. This suggests that p21 is implicated in polyploidization via suppression of CDC2 activity at mitosis. UT-7 but not HL-60 cells could incorporate [3H]thymidine in the presence of TPA, indicating the presence of megakaryocyte-specific licensing factor to allow DNA replication during differentiation. Taking these data together, we propose that megakaryocytic differentiation consists of two distinct processes, polyploidization and functional maturation, and that these two processes are independently regulated. |
| Databáze: | OpenAIRE |
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