Retinoic acid regulates C/EBP homologous protein expression (CHOP), which negatively regulates myeloid target genes
| Autor: | Dorothy J. Park, Peter T. Vuong, Sigal Gery, H. Phillip Koeffler, Doris Y. Chih, Nathan A. Lemp |
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| Rok vydání: | 2004 |
| Předmět: |
Acute promyelocytic leukemia
DNA Complementary HL60 Immunology Retinoic acid HL-60 Cells Tretinoin Biology CHOP Polymerase Chain Reaction Biochemistry chemistry.chemical_compound hemic and lymphatic diseases Gene expression medicine Humans RNA Messenger Cell Biology Hematology medicine.disease Molecular biology Gene Expression Regulation Neoplastic chemistry CDNA Subtraction CCAAT-Enhancer-Binding Proteins Signal transduction Transcription Factor CHOP DNA Damage Transcription Factors medicine.drug |
| Zdroj: | Blood. 104:3911-3917 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Retinoic acid (RA) promotes granulocytic differentiation of normal hematopoietic cells and acute promyelocytic leukemia (APL) blasts by transcriptional modulation of myeloid regulatory genes. In this study, we have identified the C/EBP homologous protein (CHOP) as a novel retinoid-responsive gene using a polymerase chain reaction (PCR)-based cDNA subtraction method. All-trans retinoic acid (ATRA) induced a biphasic expression of CHOP mRNA in the NB4 and HL60 AML cell lines. Levels of CHOP expression increased within 1 hour of exposure to ATRA. ATRA expression became nearly absent between 6 and 24 hours, and a second phase of induction occurred after 48 hours. Retinoid-dependent regulation of CHOP expression was also observed in normal human neutrophils but not in peripheral blood mononuclear cells. In addition, retinoid-dependent regulation of CHOP expression was not observed in retinoid-nonresponsive cell lines HL60R and NB4-R2. CHOP expression was regulated at the transcriptional level and was independent of new protein synthesis. CHOP heterodimerized with C/EBPϵ and negatively regulated the myeloid-specific gene lactoferrin. Furthermore, CHOP transcriptionally inhibited C/EBPα- and C/EBPϵ-dependent induction of secondary granule gene expression. RA signaling in granulocytic differentiation involves regulated expression of CHOP and C/EBPϵ in a coordinated fashion. (Blood. 2004;104:3911-3917) |
| Databáze: | OpenAIRE |
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