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Published online 16 January 2001. doi:10.1083/jcb.152.2.275
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© The Rockefeller University Press, 0021-9525/2001/1/275/ $5.00
The Journal of Cell Biology, Volume 152, Number 2, January 22, 2001 275-288

Original Article

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

Akira Kawasakia, Itaru Matsumuraa, Jun-ichiro Miyagawab, Sachiko Ezoea, Hirokazu Tanakaa, Yasuhiko Teradac, Masaaki Tatsukad, Takashi Machiia, Hiroshi Miyazakie, Yusuke Furukawaf, and Yuzuru Kanakuraa
a Department of Hematology/Oncology, Osaka University Medical School, Osaka 565-0871, Japan
b Department of Internal Medicine and Molecular Science, Osaka University Medical School, Osaka 565-0871, Japan
c Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138
d Department of Regulatory Radiobiology, Research Institution for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734, Japan
e Pharmaceutical Research Laboratory, Kirin Brewery Company, Ltd., Gunma 370-1202, Japan
f Division of Hemopoiesis, Institute of Hematology, Jichi Medical School, Tochigi 329-04, Japan

Correspondence to: Itaru Matsumura, Department of Hematology and Oncology, Osaka University Medical School, 2-2, Yamada-oka, Suita, Osaka 565-0871, Japan. Tel:81-66-87-93-871 Fax:81-66-87-93-879 E-mail:matumura{at}bldon.med.osaka-u.ac.jp.

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.

Key Words: AIM-1, STK15, polyploidization, megakaryocyte, cell cycle


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