title: During differentiation of the monocytic cell line U937, Pur alpha mediates induction of the CD11c beta 2 integrin gene promoter.
abstract: CD11c is a member of the beta(2) integrin family of adhesion molecules that, together with CD18, forms a heterodimeric receptor on the surface of myeloid, NK, dendritic, and certain leukemic, lymphoma, and activated lymphoid cells. Monocytic differentiation is associated with an induction of both CD11c and CD18 gene expression. The resulting CD11c/CD18 receptor mediates firm adhesion to the vascular endothelium, transendothelial migration, chemotaxis, and phagocytosis. Monocytic differentiation can be mimicked in vitro by treatment of the promonocytic cell line U937 with PMA. Recently, we reported that in U937 cells, expression of the CD11c gene is controlled by an unidentified transcription factor that binds ssDNA. This finding suggested that DNA secondary structure plays an important role in controlling the CD11c gene and prompted us to search for additional ssDNA-binding activities with which this gene interacts. In this study, we report that in U937 cells, expression of the CD11c gene is mediated by the ssDNA-binding protein Puralpha. During PMA-induced differentiation, the ability of Puralpha to activate the CD11c promoter in U937 cells increases, as does that of Sp1. Together, these increases in the functional activity of both Puralpha and Sp1 combine to induce CD11c expression.
authors.affiliation: Renal Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. shelley@receptor.mgh.harvard.edu
authors.forename: C Simon
authors.initials: CS
authors.lastname: Shelley
authors.forename: Jens M
authors.initials: JM
authors.lastname: Teodoridis
authors.forename: Heiyoung
authors.initials: H
authors.lastname: Park
authors.forename: Omid C
authors.initials: OC
authors.lastname: Farokhzad
authors.forename: Erwin P
authors.initials: EP
authors.lastname: Böttinger
authors.forename: M Amin
authors.initials: MA
authors.lastname: Arnaout
mesh_terms: D001483:Base Sequence; D018821:CD18 Antigens / Q000096:biosynthesis / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000276:immunology*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D016329:Sp1 Transcription Factor / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors; D020298:U937 Cells
chemical_list: D018821:CD18 Antigens; D017362:Cyclic AMP Response Element-Binding Protein; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D016167:Integrin alphaXbeta2; C501130:PURA protein, human; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors