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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Adachi, M. Articles by Sherr, C. J. Search for Related Content PubMed PubMed Citation Articles by Adachi, M. Articles by Sherr, C. J. Related Collections Hematopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Features of Macrophage Differentiation Induced by p19INK4d, a Specific Inhibitor of Cyclin D-Dependent Kinases Masashi Adachi, Martine F. Roussel, Karin Havenith, and Charles J. Sherr From the Howard Hughes Medical Institute, and the Departments of Tumor Cell Biology and Immunology, St Jude Children's Research Hospital, Memphis, TN. The mitogen-dependent induction of cyclin D-dependent kinase activity is required for cells to enter the DNA synthetic (S) phase of their division cycle. Immature 32Dcl3 myeloid cells (32D) proliferating in the presence of interleukin-3 (IL-3) normally express cyclins D2 and D3, which assemble into binary holoenzyme complexes with their catalytic subunits, CDK4 and CDK6. When 32D cells are switched to medium containing granulocyte colony-stimulating factor (G-CSF ) instead of IL-3, D-type cyclins are degraded and, in the absence of their associated kinase activity, the cells arrest in the first gap phase (G1 ) of the cell cycle and differentiate to neutrophils. We derived 32D cells in which the expression of p19INK4d, a specific polypeptide inhibitor of CDK4 and CDK6, is regulated by the heavy metal-inducible sheep metallothionein promoter. Induction of p19INK4d in response to zinc prolonged cell survival in the absence of growth factor treatment. When maintained in medium containing both IL-3 and zinc, these cells lost cyclin D-dependent kinase activity, underwent G1 phase arrest, and acquired certain morphologic, antigenic, and functional properties of mononuclear phagocytes. Cells induced to express p19INK4d did not synthesize receptors for macrophage colony-stimulating factor (M-CSF/CSF-1) and reverted to an immature myeloid phenotype when shifted back into medium containing IL-3 alone. These cells exhibited accelerated differentiation to neutrophils in response to G-CSF but also gave rise to macrophage-like cells when maintained in medium containing both G-CSF and zinc. Therefore, the acquisition of macrophage properties in response to zinc treatment neither depended upon IL-3 nor upon G1 phase arrest per se and instead reflects some ability of p19INK4d, and presumably cyclin D-dependent kinases, to affect myeloid differentiation. Blood, Vol. 90 No. 1 (July 1), 1997: pp. 126-137 © 1997 by The American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Gilles, R. Guieze, D. Bluteau, V. Cordette-Lagarde, C. Lacout, R. Favier, F. Larbret, N. Debili, W. Vainchenker, and H. Raslova P19INK4D links endomitotic arrest and megakaryocyte maturation and is regulated by AML-1 Blood, April 15, 2008; 111(8): 4081 - 4091. [Abstract] [Full Text] [PDF] E. Sicinska, Y.-M. Lee, J. Gits, H. Shigematsu, Q. Yu, V. I. Rebel, Y. Geng, C. J. Marshall, K. Akashi, D. M. Dorfman, et al. 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