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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 Hsieh, F. F. Articles by Kelley, L. L. Search for Related Content PubMed PubMed Citation Articles by Hsieh, F. F. Articles by Kelley, L. L. Related Collections Hematopoiesis and Stem Cells Red Cells Cell Cycle Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 October 2000, Vol. 96, No. 8, pp. 2746-2754 HEMATOPOIESIS Cell cycle exit during terminal erythroid differentiation is associated with accumulation of p27Kip1 and inactivation of cdk2 kinase Fen F. Hsieh, Lou Ann Barnett, Wayne F. Green, Karen Freedman, Igor Matushansky, Arthur I. Skoultchi, and Linda L. Kelley From the Departments of Pathology/Division of Cell Biology and Immunology and Medicine/Division of Hematology, University of Utah School of Medicine and Huntsman Cancer Institute, Salt Lake City, UT; and the Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY. Progression through the mammalian cell cycle is regulated by cyclins, cyclin- dependent kinases (CDKs), and cyclin-dependent kinase inhibitors (CKIs). The function of these proteins in the irreversible growth arrest associated with terminally differentiated cells is largely unknown. The function of Cip/Kip proteins p21Cip1 and p27Kip1 during erythropoietin-induced terminal differentiation of primary erythroblasts isolated from the spleens of mice infected with the anemia-inducing strain of Friend virus was investigated. Both p21Cip1 and p27Kip1 proteins were induced during erythroid differentiation, but only p27Kip1 associated with the principal G1 CDKscdk4, cdk6, and cdk2. The kinetics of binding of p27Kip1 to CDK complexes was distinct in that p27Kip1 associated primarily with cdk4 (and, to a lesser extent, cdk6) early in differentiation, followed by subsequent association with cdk2. Binding of p27Kip1 to cdk4 had no apparent inhibitory effect on cdk4 kinase activity, whereas inhibition of cdk2 kinase activity was associated with p27Kip1 binding, accumulation of hypo-phosphorylated retinoblastoma protein, and G1 growth arrest. Inhibition of cdk4 kinase activity late in differentiation resulted from events other than p27Kip1 binding or loss of cyclin D from the complex. The data demonstrate that p27Kip1 differentially regulates the activity of cdk4 and cdk2 during terminal erythroid differentiation and suggests a switching mechanism whereby cdk4 functions to sequester p27Kip1 until a specified time in differentiation when cdk2 kinase activity is targeted by p27Kip1 to elicit G1 growth arrest. Further, the data imply that p21Cip1 may have a function independent of growth arrest during erythroid differentiation. © 2000 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] J. Fang, M. Menon, W. Kapelle, O. Bogacheva, O. Bogachev, E. Houde, S. 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