c-Myc inhibits CD11a and CD11c leukocyte integrin promoters.
Eur J Immunol
; 30(9): 2465-71, 2000 Sep.
Article
en En
| MEDLINE
| ID: mdl-11009078
The 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 beta1 and beta2 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) 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 absence of additional upstream cisacting 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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Integrina alfaXbeta2
/
Antígeno-1 Asociado a Función de Linfocito
/
Proteínas Proto-Oncogénicas c-myc
/
Regiones Promotoras Genéticas
Límite:
Humans
Idioma:
En
Revista:
Eur J Immunol
Año:
2000
Tipo del documento:
Article
País de afiliación:
España
Pais de publicación:
Alemania