Mutations in FL5.12 cells conferring resistance to apoptosis induced by interleukin-3 deprivation.
In an attempt to dissect the signal pathway in which Bax increases cellular responses to apoptotic stimuli and leads to the activation of the caspase cascade, we mutated FL5.12 Bax CL16 cells with a chemical mutagen. In this report we characterize two mutant clones, FL5.12 ms1 and m3. Both clones are resistant to IL-3 deprivation exhibiting no changes in mitochondrial membrane potential, annexin V and propidium iodide binding. FL5.12 ms1 is also resistant to staurosporine and anti-Fas antibody. In cell fusion experiments m3 behaves genetically dominant and ms1 is recessive. The results suggest that m3 has a mutation in a specific function upstream of Bax, while ms1 has a mutational block in the general pathway downstream of the 'Bcl-2 checkpoint'.
Zhang
H
H
Novartis Pharma AG, Oncology, Molecular Genetics, CH-4002 Basel, Switzerland.
Brandt
R
R
Heim
J
J
Meyhack
B
B
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D006412:Hematopoietic Stem Cells / Q000502:physiology; D007377:Interleukin-3 / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases