Downregulation of an AIM-1 Kinase Couples with Megakaryocytic Polyploidization of Human Hematopoietic Cells

• Published in: The Journal of cell biology Vol. 152; no. 2; pp. 275 - 287
• Main Authors: Kawasaki, Akira, Matsumura, Itaru, Miyagawa, Jun-ichiro, Ezoe, Sachiko, Tanaka, Hirokazu, Terada, Yasuhiko, Tatsuka, Masaaki, Machii, Takashi, Miyazaki, Hiroshi, Furukawa, Yusuke, Kanakura, Yuzuru
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 22.01.2001; The Rockefeller University Press
• Subjects: AIM-1 kinase; Animals; Aurora Kinase A; Aurora Kinases; Bone marrow cells; Bone Marrow Cells - cytology; Cell cycle; Cell Cycle - physiology; Cell Division; Cell Line; Cell lines; Cells; Cells, Cultured; Cellular biology; Cultured cells; Cyclins; DNA Replication; Erythropoiesis - physiology; Female; Gene Expression Regulation, Enzymologic; Genes, ras; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - physiology; Humans; Interleukin-3 - pharmacology; K562 cells; Megakaryocytes; Megakaryocytes - cytology; Megakaryocytes - drug effects; Megakaryocytes - physiology; megakaryopoiesis; Mice; Mice, Inbred C57BL; Mitosis; Original; Phorbol Esters - pharmacology; Polyploidy; Protein Kinases - genetics; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Recombinant Proteins - pharmacology; RNA, Messenger - genetics; Stem Cell Factor - pharmacology; STK15 protein; thrombopoietin; Thrombopoietin - pharmacology; Transcription, Genetic
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.152.2.275

During the late phase of megakaryopoiesis, megakaryocytes undergo polyploidization, which is characterized by DNA duplication without concomitant cell division. However, it remains unknown by which mechanisms this process occurs. AIM-1 and STK15 belong to the Aurora/increase-in-ploidy (Ipl)1 serine/threonine kinase family and play key roles in mitosis. In a human interleukin-3-dependent cell line, F-36P, the expressions of AIM-1 and STK15 mRNA were specifically observed at G2/M phase of the cell cycle during proliferation. In contrast, the expressions of AIM-1 and STK15 were continuously repressed during megakaryocytic polyploidization of human erythro/megakaryocytic cell lines (F-36P, K562, and CMK) treated with thrombopoietin, activated ras (H-rasG12V), or phorbol ester. Furthermore, their expressions were suppressed during thrombopoietin-induced polyploidization of normal human megakaryocytes. Activation of AIM-1 by the induced expression of AIM-1(wild-type) canceled TPA-induced polyploidization of K562 cells significantly, whereas that of STK15 did not. Moreover, suppression of AIM-1 by the induced expression of AIM-1 (K/R, dominant-negative type) led to polyploidization in 25% of K562 cells, whereas STK15(K/R) showed no effect. Also, the induced expression of AIM-1(K/R) in CMK cells provoked polyploidization up to 32N. These results suggested that downregulation of AIM-1 at M phase may be involved in abortive mitosis and polyploid formation of megakaryocytes.