E3, a hematopoietic-specific transcript directly regulated by the retinoic acid receptor alpha
Autor: | LeMoyne Mueller, Steven J. Collins, Linda M. Scott |
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Rok vydání: | 1996 |
Předmět: |
Acute promyelocytic leukemia
Myeloid Cellular differentiation Immunology Response element Retinoic acid Cell Biology Hematology Biology medicine.disease Biochemistry Molecular biology chemistry.chemical_compound Retinoic acid receptor medicine.anatomical_structure chemistry Retinoic acid receptor alpha medicine Myelopoiesis |
Zdroj: | Blood. 88:2517-2530 |
ISSN: | 1528-0020 0006-4971 |
DOI: | 10.1182/blood.v88.7.2517.bloodjournal8872517 |
Popis: | Retinoic acid (RA)-induced maturation mediated by the retinoic acid receptor alpha (RAR alpha) has been implicated in myeloid development. We have used differential hybridization analysis of a cDNA library constructed from the murine RA-inducible MPRO promyelocyte cell line to identify immediate-early genes induced by RA during granulocytic differentiation. E3, one of nine sequences identified, was upregulated in an immediate-early manner, with transcript levels peaking after 60 minutes exposure to RA. E3 transcripts were RA-inducible in HL60 cells, but not in an RA-resistant subclone, HL60R, that harbors a mutated RAR alpha gene. However, when HL60R cells were transduced with a functional copy of the RAR alpha gene, RA induced a 10-fold increase in E3 mRNA levels. E3 transcripts are present in the myeloid, B-lymphoid, and erythroid lineages, absent in nonhematopoietic cells, and encode a highly hydrophobic, potentially phosphorylated polypeptide of unknown function with significant homology to a putative protein expressed in myeloid cells. The murine E3 promoter harbors a single bipartite retinoic acid response element which in transient transfection assays conferred RA sensitivity. These results indicate that E3 is a hematopoietic-specific gene that is an immediate target for the activated RAR alpha during myelopoiesis. |
Databáze: | OpenAIRE |
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