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c-Myc inhibits CD11a and CD11c leukocyte integrin promoters

AuthorsLópez-Rodríguez, Cristina; Delgado, M. Dolores ; Puig-Kröger, Amaya ; Nueda, Arsenio; Muñoz, Eduardo; León, Javier ; Bernabéu, Carmelo ; Corbí, Angel L.
KeywordsCD11c promoter
Issue Date2000
CitationEuropean Journal of Immunology 30(9): 2465-2471 (2000)
AbstractThe c-Myc transcription factor is an important regulator of cell growth and differentiation, and its gene repression ability seems to play a key role in Myc-mediated cellular transformation. Since Myc overexpression has been associated with reduced expression of β1 and β2 integrins, we have investigated the role of c-Myc on CD11a and CD11c transcription. c-Myc inhibited CD11a and CD11c integrin promoter activity in co-transfection experiments, and similar repression was obtained in cells where c-Myc expression (KmycB) or activity (Rat-1 c-MycER(TM)) is inducible. The c-Myc repression on the CD11c promoter was independent of the USF-binding site (USF-150), other putative Myc-binding elements, or the integrity of the initiator (Inr)-like sequence present at the major transcriptional start site. Analysis of deletion and mutant promoter constructs revealed that, in the absense of additional upstream cis-acting elements, an AP-1-binding site at -60 (AP1-60) is required for c-Myc repressor activity. The c-Myc repressor activity on both integrin promoters was abrogated by deletion of c-Myc residues 106-143, a domain involved in Inr-dependent transcriptional repression. These results demonstrate a direct effect of c-Myc on integrin gene transcription and suggest the existence of a c-Myc-dependent mechanism for coupling leukocyte integrin expression to the cell proliferative state.
Identifiersissn: 0014-2980
e-issn: 1521-4141
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