Subcellular and cell-cycle expression profiles of CDK-inhibitors in normal differentiating myeloid cells.
A central question in hematopoiesis is how cell-cycling behavior changes during the emergence of the differentiated state. To further understand what genetic regulators might couple proliferation status to differentiation, we studied the expression of the cell-cycle inhibitors p21 and p27 during the in vitro differentiation of normal CD34(+) blast cells along the myeloid lineage. We find p27 but not p21 to be expressed in freshly harvested resting CD34(+) cells. Thereafter, p21 levels peak concurrent with cellular proliferation and then decline in expression as cells undergo terminal differentiation. In contrast, p27 levels are fairly constant but the subcellular localization of p27 changes from nuclear expression to predominantly cytoplasmic expression and finally to perinuclear localization at progressive stages of differentiation. This report discusses the implications of these findings.
Yaroslavskiy
B
B
Departments of Medicine and Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Watkins
S
S
Donnenberg
A D
AD
Patton
T J
TJ
Steinman
R A
RA
D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D019925:Cyclin A / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D016213:Cyclins / Q000235:genetics*; D004791:Enzyme Inhibitors; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D013347:Subcellular Fractions / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D015703:Antigens, CD; D018952:Antigens, CD34; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019925:Cyclin A; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases