Depletion of the oncoprotein Bcl-3 induces centrosome amplification and aneuploidy in cancer cells.
Bcl-3 is an atypical member of the inhibitor of NF-kappa B family of proteins since it can function as a coactivator of transcription. Although this oncogene was described in leukemia, it is overexpressed in a number of solid tumors as well. The oncogenic potential of Bcl-3 has been associated with its capacity to increase proliferation by means of activating the cyclin D1 promoter and to its antiapoptotic role mediated by the inhibiton of p53 activity. In the course of dissecting these properties, we found that depleting Bcl-3 protein using shRNAs induce a decrease of proliferation and clonogenic survival associated with the induction of multinucleation and increased ploidy. These effects were associated with a DNA damage response, a delay in G2/M checkpoint and the induction of centrosome amplification.
Zamora
Ruben
R
Biotechnology Unit, Grupo Farmacéutico Neolpharma, Mexico City, Mexico.
Espinosa
Magali
M
Ceballos-Cancino
Gisela
G
Segura
Blanca
B
Maldonado
Vilma
V
Melendez-Zajgla
Jorge
J
D000782:Aneuploidy; D000081242:B-Cell Lymphoma 3 Protein; D002453:Cell Cycle; D018385:Centrosome; D019938:Cyclin D1 / Q000235:genetics; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D019938:Cyclin D1