End-stage differentiation of neutrophil granulocytes in vivo is accompanied by up-regulation of p27kip1 and down-regulation of CDK2, CDK4, and CDK6.
Research output: Contribution to journal › Journal article › Research › peer-review
The in vivo expression profiles of cell-cycle proteins regulating G1-to-S-phase transition were determined in three neutrophil precursor populations from human bone marrow: myeloblasts (MBs) and promyelocytes (PMs); myelocytes (MCs) and metamyelocytes (MMs); and band cells (BCs) and segmented neutrophil cells (SCs) and in mature polymorphonuclear neutrophils (PMNs) from peripheral blood. Complete cell-cycle arrest was observed in BCs/SCs and PMNs. Cyclins D1, D2, and D3 were found to be down-regulated during granulopoiesis, whereas a slight increase of cyclin E was seen. In contrast, cyclin-dependent kinase (CDK)2, -4, and -6 were down-regulated from the MC/MM stages and onward. The transcript levels of CDK2, -4, and -6 were concurrently down-regulated. As the only CDK inhibitor, p27kip1 protein and mRNA expression were up-regulated in MCs/MMs and reached peak levels in PMNs. Protein expression of retinoblastoma protein and the related pocket proteins p107 and p130 was down-regulated from the MC/MM stages and onward. This is the first report to describe expression levels of cell-cycle proteins during granulopoiesis in vivo, and it strongly contrasts the observations made in cell-culture systems in vitro.
Original language | English |
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Journal | Journal of Leukocyte Biology |
Volume | 75 |
Issue number | 3 |
Pages (from-to) | 569-78 |
Number of pages | 9 |
ISSN | 0741-5400 |
DOIs | |
Publication status | Published - 2003 |
Externally published | Yes |
Bibliographical note
Keywords: CDC2-CDC28 Kinases; Cell Cycle Proteins; Cell Differentiation; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Cyclin-Dependent Kinase Inhibitor p27; Cyclin-Dependent Kinases; Cyclins; G1 Phase; Gene Expression Profiling; Gene Expression Regulation; Humans; Leukopoiesis; Neutrophils; Proto-Oncogene Proteins; S Phase; Tumor Suppressor Proteins
ID: 6015228