Downregulation of an AIM-1 kinase couples with megakaryocytic polyploidization of human hematopoietic cells

Akira Kawasaki, Itaru Matsumura, Jun Ichiro Miyagawa, Sachiko Ezoe, Hirokazu Tanaka, Yasuhiko Terada, Masaaki Tatsuka, Takashi Machii, Hiroshi Miyazaki, Yusuke Furukawa, Yuzuru Kanakura

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)275-287
Number of pages13
JournalJournal of Cell Biology
Volume152
Issue number2
DOIs
Publication statusPublished - 2001 Jan 22
Externally publishedYes

Fingerprint

Megakaryocytes
Cell Division
Thrombopoietin
Phosphotransferases
Down-Regulation
K562 Cells
Mitosis
Cell Line
Polyploidy
Ploidies
Interleukin-3
G2 Phase
Protein-Serine-Threonine Kinases
Phorbol Esters
Cell Cycle
Messenger RNA
DNA

Keywords

  • AIM-1
  • Cell cycle
  • Megakaryocyte
  • Polyploidization
  • STK15

ASJC Scopus subject areas

  • Cell Biology

Cite this

Downregulation of an AIM-1 kinase couples with megakaryocytic polyploidization of human hematopoietic cells. / Kawasaki, Akira; Matsumura, Itaru; Miyagawa, Jun Ichiro; Ezoe, Sachiko; Tanaka, Hirokazu; Terada, Yasuhiko; Tatsuka, Masaaki; Machii, Takashi; Miyazaki, Hiroshi; Furukawa, Yusuke; Kanakura, Yuzuru.

In: Journal of Cell Biology, Vol. 152, No. 2, 22.01.2001, p. 275-287.

Research output: Contribution to journalArticle

Kawasaki, A, Matsumura, I, Miyagawa, JI, Ezoe, S, Tanaka, H, Terada, Y, Tatsuka, M, Machii, T, Miyazaki, H, Furukawa, Y & Kanakura, Y 2001, 'Downregulation of an AIM-1 kinase couples with megakaryocytic polyploidization of human hematopoietic cells', Journal of Cell Biology, vol. 152, no. 2, pp. 275-287. https://doi.org/10.1083/jcb.152.2.275
Kawasaki, Akira ; Matsumura, Itaru ; Miyagawa, Jun Ichiro ; Ezoe, Sachiko ; Tanaka, Hirokazu ; Terada, Yasuhiko ; Tatsuka, Masaaki ; Machii, Takashi ; Miyazaki, Hiroshi ; Furukawa, Yusuke ; Kanakura, Yuzuru. / Downregulation of an AIM-1 kinase couples with megakaryocytic polyploidization of human hematopoietic cells. In: Journal of Cell Biology. 2001 ; Vol. 152, No. 2. pp. 275-287.
@article{51abf0874561416b9080a9b2545758fb,
title = "Downregulation of an AIM-1 kinase couples with megakaryocytic polyploidization of human hematopoietic cells",
abstract = "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.",
keywords = "AIM-1, Cell cycle, Megakaryocyte, Polyploidization, STK15",
author = "Akira Kawasaki and Itaru Matsumura and Miyagawa, {Jun Ichiro} and Sachiko Ezoe and Hirokazu Tanaka and Yasuhiko Terada and Masaaki Tatsuka and Takashi Machii and Hiroshi Miyazaki and Yusuke Furukawa and Yuzuru Kanakura",
year = "2001",
month = "1",
day = "22",
doi = "10.1083/jcb.152.2.275",
language = "English",
volume = "152",
pages = "275--287",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "2",

}

TY - JOUR

T1 - Downregulation of an AIM-1 kinase couples with megakaryocytic polyploidization of human hematopoietic cells

AU - Kawasaki, Akira

AU - Matsumura, Itaru

AU - Miyagawa, Jun Ichiro

AU - Ezoe, Sachiko

AU - Tanaka, Hirokazu

AU - Terada, Yasuhiko

AU - Tatsuka, Masaaki

AU - Machii, Takashi

AU - Miyazaki, Hiroshi

AU - Furukawa, Yusuke

AU - Kanakura, Yuzuru

PY - 2001/1/22

Y1 - 2001/1/22

N2 - 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.

AB - 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.

KW - AIM-1

KW - Cell cycle

KW - Megakaryocyte

KW - Polyploidization

KW - STK15

UR - http://www.scopus.com/inward/record.url?scp=0035931757&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035931757&partnerID=8YFLogxK

U2 - 10.1083/jcb.152.2.275

DO - 10.1083/jcb.152.2.275

M3 - Article

VL - 152

SP - 275

EP - 287

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 2

ER -