Document Detail


A Myb dependent pathway maintains Friend murine erythroleukemia cells in an immature and proliferating state.
MedLine Citation:
PMID:  11896618     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Jing Chen; Christopher S Kremer; Timothy P Bender
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oncogene     Volume:  21     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2002 Mar 
Date Detail:
Created Date:  2002-03-22     Completed Date:  2002-04-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  1859-69     Citation Subset:  IM    
Affiliation:
Department of Molecular Physiology, University of Virginia Health System, PO Box 800734, Charlottesville, Virginia, VA 22908-0734, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetamides / pharmacology
Animals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Basic-Leucine Zipper Transcription Factors
Cell Cycle Proteins*
Cell Division
DNA-Binding Proteins / genetics,  metabolism,  physiology*
Friend murine leukemia virus / physiology*
Genes, myc / physiology
Globins / genetics,  metabolism
Hemoglobins / biosynthesis
Leukemia, Erythroblastic, Acute / metabolism,  pathology*,  virology
Metallothionein / genetics
Mice
Nuclear Proteins
Phosphoproteins / physiology
Plasmids
Proto-Oncogene Proteins / physiology*
Proto-Oncogene Proteins c-myb / physiology*
RNA, Messenger / genetics,  metabolism
Repressor Proteins / physiology
Trans-Activators / physiology*
Transcription Factors*
Tumor Cells, Cultured / metabolism,  pathology,  virology
Zinc / metabolism
Grant Support
ID/Acronym/Agency:
GM55985/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Acetamides; 0/Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; 0/Basic-Leucine Zipper Transcription Factors; 0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/Hemoglobins; 0/MAD1L1 protein, human; 0/Mad1l1 protein, mouse; 0/Mybl1 protein, mouse; 0/Mybl2 protein, mouse; 0/Myc associated factor X; 0/Nuclear Proteins; 0/Phosphoproteins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-myb; 0/RNA, Messenger; 0/Repressor Proteins; 0/Trans-Activators; 0/Transcription Factors; 137468-70-3/Max protein, mouse; 3073-59-4/hexamethylene bisacetamide; 7440-66-6/Zinc; 9004-22-2/Globins; 9038-94-2/Metallothionein

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