title: A Myb dependent pathway maintains Friend murine erythroleukemia cells in an immature and proliferating state.
abstract: Friend murine erythroleukemia (MEL) cells are transformed erythroid precursors that are held in an immature and proliferating state but can be induced to differentiate in vivo by treatment with a variety of chemical agents such as N, N-hexamethylene bisacetamide (HMBA). To investigate the role of Myb proteins in maintaining MEL cells in an immature and proliferating state we have produced stable transfectants in the C19 MEL cell line that contain a dominant interfering Myb allele (MEnT) under the control of an inducible mouse metallothionein I promoter. When expression of MEnT protein was induced with ZnCl2, the stable transfectants differentiated with kinetics that were similar to wild type C19 MEL cells treated with HMBA, including induction of alpha-globin mRNA expression, assembly of hemoglobin and growth arrest. Expression of endogenous c-myb and c-myc was also decreased in response to MEnT. Expression of mad-1 mRNA was rapidly increased in response to expression of MEnT resulting in a shift from predominantly c-Myc/Max complexes to predominantly Mad/Max containing complexes. These results strongly suggest that C19 MEL cells are held in an immature and proliferating state by a pathway that is dependent on Myb activity.
authors.affiliation: Department of Molecular Physiology, University of Virginia Health System, PO Box 800734, Charlottesville, Virginia, VA 22908-0734, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Kremer
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Bender
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005622:Friend murine leukemia virus / Q000502:physiology*; D016259:Genes, myc / Q000502:physiology; D005914:Globins / Q000235:genetics / Q000378:metabolism; D006454:Hemoglobins / Q000096:biosynthesis; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000502:physiology; D010957:Plasmids; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D020598:Proto-Oncogene Proteins c-myb / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015032:Zinc / Q000378:metabolism
chemical_list: D000081:Acetamides; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006454:Hemoglobins; C501384:MAD1L1 protein, human; C501385:Mad1l1 protein, mouse; C490283:Mybl1 protein, mouse; C499306:Mybl2 protein, mouse; C067850:Myc associated factor X; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C068422:Max protein, mouse; D005914:Globins; D008668:Metallothionein; D015032:Zinc; C014026:hexamethylene bisacetamide