![]() ![]() This phosphomutant form of the protein has previously been used to show that preventing multi-site phosphorylation of ASCL1 promotes transcription factor–mediated reprogramming of embryonic ectoderm and fibroblasts into neurons ( 18). ![]() A PARP cleavage product is absent from Dox-treated ASCL1-expressing neuroblastoma cells, so the reduction in cell number cannot be attributed to an increase in apoptosis, but does indicate that elevating ASCL1 activity suppresses neuroblastoma cell proliferation.Ī phosphomutant form of ASCL1 (S-A ASCL1) can be generated by mutating all serine–proline phosphorylation sites to alanine–proline. Cell apoptosis is accompanied by cleavage of PARP, which can be readily observed after SDS PAGE separation in control neuroblastoma cells treated with the apoptotic inducer Staurosporine (Supplementary Fig. S1A) revealed that increasing WT ASCL1 progressively reduced neuroblastoma cell confluency (Supplementary Fig. Using isogenically matched ASCL1-inducible neuroblastoma lines to study the effects of different expression levels (Supplementary Fig. To explore this, we exploited the SH-SY5Y neuroblastoma cell line, which expresses a moderate level of ASCL1 protein ( 15) and is a representative model of the higher-risk ADRN disease subtype (refs. As overexpression of ASCL1 can drive ectopic noradrenergic neurogenesis in vivo ( 15), we questioned whether an increase in ASCL1 activity over the endogenous level might be sufficient to render neuroblastoma cells post-mitotic and activate morphological differentiation. Neuroblastoma cells frequently express ASCL1 ( 15), yet remain highly proliferative. ![]()
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