G1-Cdk activity is required for both proliferation and viability of cytokine-dependent myeloid and erythroid cells.
Hematopoietic cytokines are critically required for survival and cell proliferation of myeloid and erythroid progenitors. It is poorly understood how the apoptotic machinery of progenitor cells senses the absence of specific cytokines. Here we show that G1-Cdk activity is essential for cytokine-mediated viability of myeloid and erythroid progenitors. Cytokine deprivation is associated with rapid downregulation of G1-Cdk activity, cell cycle arrest, and apoptosis. Specific inhibition of G1-Cdk activity results in apoptotic cell death in the presence of saturating cytokine levels. In contrast, specific cell cycle arrest in G2/M does not affect viability. When cell proliferation is arrested by cytokine withdrawal, primary erythroid progenitors expressing v-ErbA maintain G1-Cdk activity and undergo delayed apoptosis. Cdk-inhibitors strongly enhance apoptosis in starved v-ErbA cells, indicating that sustained Cdk activity is required for protection from apoptosis by v-ErbA.
Hofmann
J F
JF
Research Institute of Molecular Pathology, Dr. Bohr Gasse 7, A-1030 Vienna, Austria.
Sykora
M
M
Redemann
N
N
Beug
H
H
D017209:Apoptosis; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D056746:Cyclin G; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D018774:Oncogene Proteins v-erbA / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D056746:Cyclin G; D016213:Cyclins; D016207:Cytokines; D018774:Oncogene Proteins v-erbA; D019253:Proto-Oncogene Proteins c-bcl-2; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases