Granulocyte-macrophage colony-stimulating factor, phorbol ester, and sodium butyrate induce the CD11c integrin gene promoter activity during myeloid cell differentiation.

2.50
Hdl Handle:
http://hdl.handle.net/2436/7743
Title:
Granulocyte-macrophage colony-stimulating factor, phorbol ester, and sodium butyrate induce the CD11c integrin gene promoter activity during myeloid cell differentiation.
Authors:
Rubio, M.A.; Lopez-Rodriguez, C.; Nueda, A.; Aller, P.; Armesilla, Angel Luis; Vega, Miguel A.; Corbí, A.L.
Abstract:
To analyze the activity of the CD11c promoter during myeloid differentiation without the limitations of transient expression systems, we have stably transfected the myeloid U937 cell line with the pCD11C361-Luc plasmid, in which the expression of the firefly luciferase cDNA is driven by the CD11c promoter region -361/+43, previously shown to confer myeloid specificity to reporter genes. The stable transfectants (U937-C361) retained the ability to differentiate in response to phorbol-ester (PMA), sodium butyrate (SB), granulocyte-macrophage colony-stimulating factor (GM-CSF), and other differentiating agents. U937-C361 differentiation correlated with increased cellular luciferase levels, showing the inducibility of the CD11c promoter during myeloid differentiation and establishing the U937-C361 cells as a suitable system for studying the myeloid differentiation-inducing capacity of cytokines, growth, factors, and other biological response modifiers. Unexpectedly, the inducibility of the CD11c gene promoter showed distinct kinetics and magnitude on the PMA-, SB-, GM-CSF-triggered differentiation. Moreover, SB synergized with either PMA or GM-CSF in enhancing both the CD11c promoter activity and the cell surface expression of p150,95 on differentiating U937 cells. Furthermore, we showed the existence of a c-Myb-binding site at -85, the importance of the -99/-61 region in the CD11c promoter inducibility during PMA- or SB-triggered differentiation, and the dependency of the GM-CSF and PMA responsiveness of the CD11c promoter on an intact AP-1-binding site located at -60. These results, together with the lack of functional effect of mutations disrupting the Sp1-and Myb-binding sites within the proximal region of the CD11c promoter, indicate that the myeloid differentiation pathways indicated by SB and phorbol esters (or GM-CSF) activate a distinct set of transcription factors and show that the myeloid differentiation-inducibility of the CD11c gene maps to the -99/-53 proximal region of the promoter.
Citation:
Blood, 86(10): 3715-3724
Publisher:
American Society of Hematology
Issue Date:
1995
URI:
http://hdl.handle.net/2436/7743
PubMed ID:
7579338
Additional Links:
http://www.bloodjournal.org/cgi/reprint/86/10/3715
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
Molecular Pharmacology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorRubio, M.A.-
dc.contributor.authorLopez-Rodriguez, C.-
dc.contributor.authorNueda, A.-
dc.contributor.authorAller, P.-
dc.contributor.authorArmesilla, Angel Luis-
dc.contributor.authorVega, Miguel A.-
dc.contributor.authorCorbí, A.L.-
dc.date.accessioned2007-01-24T14:14:07Z-
dc.date.available2007-01-24T14:14:07Z-
dc.date.issued1995-
dc.identifier.citationBlood, 86(10): 3715-3724en
dc.identifier.issn0006-4971-
dc.identifier.pmid7579338-
dc.identifier.urihttp://hdl.handle.net/2436/7743-
dc.description.abstractTo analyze the activity of the CD11c promoter during myeloid differentiation without the limitations of transient expression systems, we have stably transfected the myeloid U937 cell line with the pCD11C361-Luc plasmid, in which the expression of the firefly luciferase cDNA is driven by the CD11c promoter region -361/+43, previously shown to confer myeloid specificity to reporter genes. The stable transfectants (U937-C361) retained the ability to differentiate in response to phorbol-ester (PMA), sodium butyrate (SB), granulocyte-macrophage colony-stimulating factor (GM-CSF), and other differentiating agents. U937-C361 differentiation correlated with increased cellular luciferase levels, showing the inducibility of the CD11c promoter during myeloid differentiation and establishing the U937-C361 cells as a suitable system for studying the myeloid differentiation-inducing capacity of cytokines, growth, factors, and other biological response modifiers. Unexpectedly, the inducibility of the CD11c gene promoter showed distinct kinetics and magnitude on the PMA-, SB-, GM-CSF-triggered differentiation. Moreover, SB synergized with either PMA or GM-CSF in enhancing both the CD11c promoter activity and the cell surface expression of p150,95 on differentiating U937 cells. Furthermore, we showed the existence of a c-Myb-binding site at -85, the importance of the -99/-61 region in the CD11c promoter inducibility during PMA- or SB-triggered differentiation, and the dependency of the GM-CSF and PMA responsiveness of the CD11c promoter on an intact AP-1-binding site located at -60. These results, together with the lack of functional effect of mutations disrupting the Sp1-and Myb-binding sites within the proximal region of the CD11c promoter, indicate that the myeloid differentiation pathways indicated by SB and phorbol esters (or GM-CSF) activate a distinct set of transcription factors and show that the myeloid differentiation-inducibility of the CD11c gene maps to the -99/-53 proximal region of the promoter.en
dc.format.extent4758937 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoenen
dc.publisherAmerican Society of Hematologyen
dc.relation.urlhttp://www.bloodjournal.org/cgi/reprint/86/10/3715en
dc.subjectCD11c integrin gene promoteren
dc.subjectPhorbol esteren
dc.subjectSodium butyrateen
dc.subjectCell differentiationen
dc.subjectGranulocyte-macrophageen
dc.titleGranulocyte-macrophage colony-stimulating factor, phorbol ester, and sodium butyrate induce the CD11c integrin gene promoter activity during myeloid cell differentiation.en
dc.typeArticleen
dc.format.digYES-

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