Increased D-type cyclin expression together with decreased cdc2 activity confers megakaryocytic differentiation of a human thrombopoietin-dependent hematopoietic cell line

Itaru Matsumura, Hirokazu Tanaka, Akira Kawasaki, Junko Odajima, Hanako Daino, Koji Hashimoto, Hiroshi Wakao, Koichi Nakajima, Takashi Kato, Hiroshi Miyazaki, Yuzuru Kanakura

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

At the late phase of megakaryocytopoiesis, megakaryocytes undergo endomitosis, which is characterized by DNA replication without cell division. Although a number of cell cycle regulatory molecules have been identified, the precise roles of these molecules in megakaryocytic endomitosis are largely unknown. In a human interleukin-3-dependent cell line transfected with the thrombopoietin (TPO) receptor c-mpl (F-36P-mpl), either treatment with TPO or the overexpression of activated ras (Ha-Ras(G12V)) induced megakaryocytic maturation with polyploid formation. We found that TPO stimulation or Ha-Ras(G12v) expression led to up-regulation of cyclin D1, cyclin D2, and cyclin D3 expression. In addition, expression levels of cyclin A and cyclin B were reduced during the total course of both TPO- and Ha- Ras(G12V)-induced megakaryocytic differentiation, thereby leading to decreased cdc2 kinase activity. Neither the induced expression of cyclin D1, cyclin D2, or cyclin D3 nor the expression of a dominant negative form of cdc2 alone could induce megakaryocytic differentiation of F-36P-mpl cells. In contrast, overexpression of dominant negative cdc2 together with cyclin D1, cyclin D2, or cyclin D3 facilitated megakaryocytic differentiation in the absence of TPO. These results suggest that both D-type cyclin expression and decreased cdc2 kinase activity may participate in megakaryocytic differentiation.

Original languageEnglish
Pages (from-to)5553-5559
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number8
DOIs
Publication statusPublished - 2000 Feb 25
Externally publishedYes

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Cyclin D
Thrombopoietin
Cyclin D3
Cyclin D2
Cyclin D1
Cells
Cell Line
Phosphotransferases
Thrombopoietin Receptors
Thrombopoiesis
Cyclin B
Cyclin A
Molecules
Polyploidy
Megakaryocytes
Interleukin-3
DNA Replication
Cell Division
Cell Cycle
Up-Regulation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Increased D-type cyclin expression together with decreased cdc2 activity confers megakaryocytic differentiation of a human thrombopoietin-dependent hematopoietic cell line. / Matsumura, Itaru; Tanaka, Hirokazu; Kawasaki, Akira; Odajima, Junko; Daino, Hanako; Hashimoto, Koji; Wakao, Hiroshi; Nakajima, Koichi; Kato, Takashi; Miyazaki, Hiroshi; Kanakura, Yuzuru.

In: Journal of Biological Chemistry, Vol. 275, No. 8, 25.02.2000, p. 5553-5559.

Research output: Contribution to journalArticle

Matsumura, I, Tanaka, H, Kawasaki, A, Odajima, J, Daino, H, Hashimoto, K, Wakao, H, Nakajima, K, Kato, T, Miyazaki, H & Kanakura, Y 2000, 'Increased D-type cyclin expression together with decreased cdc2 activity confers megakaryocytic differentiation of a human thrombopoietin-dependent hematopoietic cell line', Journal of Biological Chemistry, vol. 275, no. 8, pp. 5553-5559. https://doi.org/10.1074/jbc.275.8.5553
Matsumura, Itaru ; Tanaka, Hirokazu ; Kawasaki, Akira ; Odajima, Junko ; Daino, Hanako ; Hashimoto, Koji ; Wakao, Hiroshi ; Nakajima, Koichi ; Kato, Takashi ; Miyazaki, Hiroshi ; Kanakura, Yuzuru. / Increased D-type cyclin expression together with decreased cdc2 activity confers megakaryocytic differentiation of a human thrombopoietin-dependent hematopoietic cell line. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 8. pp. 5553-5559.
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AU - Hashimoto, Koji

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