Cyclin D1 is a NF-κB corepressor.
NF-κB regulates the expression of Cyclin D1 (CD1), while RAC3 is an NF-κB coactivator that enhances its transcriptional activity. In this work, we investigated the regulatory role of CD1 on NF-κB activity. We found that CD1 inhibits NF-κB transcriptional activity through a corepressor function that can be reverted by over-expressing RAC3. In both, tumoral and non-tumoral cells, the expression pattern of RAC3 and CD1 is regulated by the cell cycle, showing a gap between the maximal expression levels of each protein. The individual increase, by transfection, of either CD1 or RAC3 enhances cell proliferation. However the simultaneous and constitutive over-expression of both proteins has an inhibitory effect. Our results suggest that the relative amounts of CD1 and RAC3, and the timing of expression of these oncogenes could tilt the balance of tumor cell proliferation in response to external signals.
Laboratorio de Biología Molecular y Apoptosis, Instituto de Investigaciones Médicas Alfredo Lanari (IDIM-CONICET), Universidad de Buenos Aires, Combatientes de Malvinas 3150, C1427ARO Buenos Aires, Argentina.
María F
MF
Rubio
Pablo N Larrosa
PN
Fernandez
Cecilia V
CV
Alvarado
L C
LC
Panelo
Marina Ruiz
MR
Grecco
Georgina P
GP
Colo
Giselle A
GA
Martínez-Noel
Sabrina M
SM
Micenmacher
Mónica A
MA
Costas
D001665:Binding Sites; D002448:Cell Adhesion; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056970:Co-Repressor Proteins / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008954:Models, Biological; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics; D020744:rac GTP-Binding Proteins / Q000378:metabolism
C530104:CCND1 protein, human; D056970:Co-Repressor Proteins; D016328:NF-kappa B; C411563:RAC3 protein, human; D019938:Cyclin D1; D004247:DNA; D020744:rac GTP-Binding Proteins