Cyclin D1 is a NF-κB corepressor

• Published in: Biochimica et biophysica acta Vol. 1823; no. 6; pp. 1119 - 1131
• Main Authors: Rubio, María F., Fernandez, Pablo N. Larrosa, Alvarado, Cecilia V., Panelo, L.C., Grecco, Marina Ruiz, Colo, Georgina P., Martínez-Noel, Giselle A., Micenmacher, Sabrina M., Costas, Mónica A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-06-2012
• Subjects: Binding Sites; Cell Adhesion; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Co-Repressor Proteins - metabolism; Cyclin D1; Cyclin D1 - metabolism; DNA - metabolism; HEK293 Cells; Humans; Models, Biological; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB; Nuclear receptor coactivator; Protein Binding; Protein Transport; rac GTP-Binding Proteins - metabolism; RAC3; Transcription, Genetic; Transcriptional Activation - genetics; Transcriptional activity; Tumor development; PMA; SRC; Cdk; Cyclin D1; ER; Tumor development; CD1; NF-κB; RAC3; HAT; Transcriptional activity; Nuclear receptor coactivator; HDAC
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2012.01.009

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.
► Cyclin D1 plays an inhibitory role over NF-κB transcriptional activity. ► The repression of NF-κB transactivation by CD1 involves a deacetylase activity. ► Cyclin D1 and the transcription factor NF-κB could be part of the same protein complex.