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Cellular stress-induced up-regulation of FMRP promotes cell survival by modulating PI3K-Akt phosphorylation cascades

DOI: 10.1186/1423-0127-18-17

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Apoptotic cell death was induced by etoposide treatment on Hela cells. After we transiently modulated FMRP expression (silencing or enhancing) by using molecular biotechnological methods such as small hairpin RNA virus-induced knock down and overexpression using transfection with FMRP expression vectors, cellular viability was measured using propidium iodide staining, TUNEL staining, and FACS analysis along with the level of activation of PI3K-Akt pathway by Western blot. Expression level of FMRP and apoptotic regulator BcL-xL was analyzed by Western blot, RT-PCR and immunocytochemistry.An increased FMRP expression was measured in etoposide-treated HeLa cells, which was induced by PI3K-Akt activation. Without FMRP expression, cellular defence mechanism via PI3K-Akt-Bcl-xL was weakened and resulted in an augmented cell death by etoposide. In addition, FMRP over-expression lead to the activation of PI3K-Akt signalling pathway as well as increased FMRP and BcL-xL expression, which culminates with the increased cell survival in etoposide-treated HeLa cells.Taken together, these results suggest that FMRP expression is an essential part of cellular survival mechanisms through the modulation of PI3K, Akt, and Bcl-xL signal pathways.Fragile X syndrome (FXS) is a well known neurodevelopmental disorder caused by loss of fragile X linked mental retardation protein (FMRP) which is encoded by Fmr1 gene [1]. FXS patients typically show a wide spectrum of cognitive and behavioral problems such as attention deficit, anxiety and mood disorder, increased risk of seizures, autistic spectrum behaviors, and mental retardation [1]. FMRP is expressed in many tissues including testis, placenta, and brain [2,3] and in a variety of cell types including HeLa [4].FMRP is a RNA binding protein, which regulates translation of target mRNAs. A wide range of potential target mRNAs have been suggested, most of which have been correlated to the regulation of synaptic function as well as neuronal deve

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