c-Myc inhibits CD11a and CD11c leukocyte integrin promoters.
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.
López-Rodríguez
C
C
Centro de Investigaciones Biológicas, CSIC, Madrid, Spain.
Delgado
M D
MD
Puig-Kröger
A
A
Nueda
A
A
Muñoz
E
E
León
J
J
Bernabéu
C
C
Corbi
A L
AL
D002460:Cell Line; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000235:genetics*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*; D020218:Response Elements
D016167:Integrin alphaXbeta2; D016169:Lymphocyte Function-Associated Antigen-1; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins