Silencing of the transcription factor KLF6 by siRNA leads to cell cycle arrest and sensitizes cells to apoptosis induced by DNA damage

D´ASTOLFO, D.; GEHRAU, R.; ANDREOLI, V.; BOCCO, J.L.; KORITSCHONER, N.P.

Bariloche-Argentina

Congreso; Combined Meetings: Gene Expression and RNA processing// Cell Biology Signalling and Alternative Splicing; 2007

International Centre for Genetic Engineering and Biotechnology (ICGEB) - Facultad de Ciencias Exactas y

KLF6 is an evolutionary conserved and ubiquitously expressed mammalian transcription factor that has been involved in cell cycle control mechanisms in normal and cancer cells. It is demonstrated here that an efficient siRNA-mediated knockdown of endogenous KLF6 inhibited the proliferation rate of different cell types by upregulating the cell cycle inhibitor p21cip1 at the transcriptional level, suggesting that KLF6 functions as a general positive regulator of cell cycle progression. We also show that KLF6 expression levels were drastically downregulated at the transcriptional level during DNA damage-induced apoptosis in a p53-independent manner. Most importantly, KLF6 loss by siRNA sensitized cells to apoptosis triggered by DNA-damaging agents. Our data that siRNA-mediated loss of KLF6 induced cell cycle arrest and additionally favored cell death supports the notion that KLF6 plays a dual role by positively contributing to cell proliferation and also as an anti-apoptotic factor