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PMID: 9566892 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

c-Maf interacts with c-Myb to regulate transcription of an early myeloid gene during differentiation.

Molecular and cellular biology ·Vol. 18 ·No. 5 ·1998-05-00 ·Pages 2729-37

Hedge SP, Kumar A, Kurschner C, Shapiro LH

Abstract

The MafB transcriptional activator plays a pivotal role in regulating lineage-specific gene expression during hematopoiesis by repressing Ets-1-mediated transcription of key erythroid-specific genes in myeloid cells. To determine the effects of Maf family proteins on the transactivation of myeloid-specific genes in myeloid cells, we tested the ability of c-Maf to influence Ets-1- and c-Myb-dependent CD13/APN transcription. Expression of c-Maf in human immature myeloblastic cells inhibited CD13/APN-driven reporter gene activity (85 to 95% reduction) and required the binding of both c-Myb and Ets, but not Maf, to the promoter fragment. c-Maf's inhibition of CD13/APN expression correlates with its ability to physically associate with c-Myb. While c-Maf mRNA and protein levels remain constant during myeloid differentiation, formation of inhibitory Myb-Maf complexes was developmentally regulated, with their levels being highest in immature myeloid cell lines and markedly decreased in cell lines representing later developmental stages. This pattern matched that of CD13/APN reporter gene expression, indicating that Maf modulation of c-Myb activity may be an important mechanism for the control of gene transcription during hematopoietic cell development.

MeSH Terms
Binding Sites Bone Marrow Cells/metabolism CD13 Antigens/biosynthesis,genetics Cell Differentiation Cell Line DNA-Binding Proteins/metabolism Hematopoiesis/genetics Humans Protein Binding Proto-Oncogene Protein c-ets-1 Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-ets Proto-Oncogene Proteins c-maf Proto-Oncogene Proteins c-myb Stem Cells/metabolism Trans-Activators/metabolism Transcription Factors/metabolism Transcription, Genetic
Chemicals
DNA-Binding Proteins ETS1 protein, human MAF protein, human Proto-Oncogene Protein c-ets-1 Proto-Oncogene Proteins Proto-Oncogene Proteins c-ets Proto-Oncogene Proteins c-maf Proto-Oncogene Proteins c-myb Trans-Activators Transcription Factors CD13 Antigens
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hedge S P
Department of Experimental Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Kumar A
Kurschner C
Shapiro L H
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.5.2729
Published
1998-05-00
Pages
2729-37
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC110652
Subset
IM
Grants
NCI NIH HHS · CA-21765 · United States
NCI NIH HHS · CA-70909 · United States
External Links
PubMed source DOI: 10.1128/MCB.18.5.2729 PMC Full Text View journal details
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