BOCCO JOSE LUIS
Congresos y reuniones científicas
Título:
Silencing endogenous KLF6 gene reveals a new function as a positive regulator of cell proliferation.
Autor/es:
D’ASTOLFO, DIEGO; GEHRAU, RICARDO; BOCCO, JOSE LUIS; KORITSCHONER, NICOLAS
Lugar:
Pinamar, Buenos Aires. ARGENTINA
Reunión:
Congreso; XLI Reunión Anual de la Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular. 10th Congress Panamerican Association for Biochemistry and Molecular Biology. 20th Reunión Anual Sociedad Argentina de Neuroquímica.; 2005
Institución organizadora:
Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular.
Resumen:
The Krüppel-like transcription Factor KLF6 is involved in mechanisms controlling normal cell proliferation and tumor formation. This work aimed at characterizing cell cycle control pathways that are regulated by KLF6 and thus should be responsible for the KLF6 induced phenotypes. Here we report an efficient inhibition of endogenous KLF6 expression by employing several small interfering RNAs (siRNAs) targeted to different regions of KLF6 mRNA. Up to 90% of KLF6 knock-down was achieved in COS-7 cells. BrdU incorporation analysis indicated that KLF6- defficient cells slowed their proliferation rates. This effect was seen under different experimental conditions (0.1%-4% of fetal serum). Interestingly, KLF6 knock-down increased the cyclin-dependent kinase inhibitor p21cip1/waf and reduced the phosphorylation status of the retinoblastoma (Rb) protein. To test the possibility that p21 transcription might be regulated by KLF6, the promoter regions of p21 were analyzed in transfection experiments. It was determined that the knock-down of KLF6 increased the transcriptional activity of p21 gene. In conclusion, these data position the transcription factor KLF6 as a positive regulator of cell cycle progression by repressing p21 expression.