RRC ID 39820
Author Matsumura I, Tanaka H, Kawasaki A, Odajima J, Daino H, Hashimoto K, Wakao H, Nakajima K, Kato T, Miyazaki H, Kanakura Y.
Title Increased D-type cyclin expression together with decreased cdc2 activity confers megakaryocytic differentiation of a human thrombopoietin-dependent hematopoietic cell line.
Journal J Biol Chem
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.
Volume 275(8)
Pages 5553-9
Published 2000-2-25
DOI 10.1074/jbc.275.8.5553
PMID 10681535
MeSH CDC2 Protein Kinase / metabolism* Cell Cycle / drug effects Cell Differentiation Cyclin D Cyclin D1 / metabolism Cyclin D2 Cyclin D3 Cyclins / metabolism Cyclins / physiology* DNA, Complementary / metabolism Flow Cytometry Genes, Dominant Hematopoietic Stem Cells / cytology* Humans Isopropyl Thiogalactoside / pharmacology Megakaryocytes / cytology* Plasmids Proto-Oncogene Proteins p21(ras) / metabolism Recombinant Proteins / metabolism Thrombopoietin / metabolism* Thrombopoietin / pharmacology Time Factors Tumor Cells, Cultured
IF 4.106
Times Cited 35
Human and Animal Cells