Functional whole-genome analysis identifies Polo-like kinase 2 and poliovirus receptor as essential for neuronal differentiation upstream of the negative regulator alphaB-crystallin
| Autor: | Goutopoulos Andreas, Helene Peixoto, Christian Rommel, Mohanraj Dhanabal, Cristina Draghetti, Montserrat Camps, Francisca Zanoguera, Hadi Abderrahim, Alessandro Di Cara, David J. Fischer, Marie Laure Curchod, Catherine Salvat, Chloé Vignaud |
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| Rok vydání: | 2009 |
| Předmět: |
Cellular differentiation
Blotting Western Polo-like kinase Biology Protein Serine-Threonine Kinases Biochemistry Mice Nerve Growth Factor Gene silencing Animals Humans RNA Messenger Genomics Proteomics and Bioinformatics Protein kinase A Molecular Biology Cells Cultured Oligonucleotide Array Sequence Analysis Neurons Genome Kinase Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Computational Biology alpha-Crystallin B Chain Cell Differentiation Cell Biology Molecular biology Rats Nerve growth factor nervous system Receptors Virus Janus kinase Poliovirus Receptor |
| Zdroj: | The Journal of biological chemistry. 284(46) |
| ISSN: | 1083-351X |
| Popis: | This study aimed at identifying transcriptional changes associated to neuronal differentiation induced by six distinct stimuli using whole-genome microarray hybridization analysis. Bioinformatics analyses revealed the clustering of these six stimuli into two categories, suggesting separate gene/pathway dependence. Treatment with specific inhibitors demonstrated the requirement of both Janus kinase and microtubule-associated protein kinase activation to trigger differentiation with nerve growth factor (NGF) and dibutyryl cAMP. Conversely, activation of protein kinase A, phosphatidylinositol-3-kinase alpha, and mammalian target of rapamycin, although required for dibutyryl cAMP-induced differentiation, exerted a negative feedback on NGF-induced differentiation. We identified Polo-like kinase 2 (Plk2) and poliovirus receptor (PVR) as indispensable for NGF-driven neuronal differentiation and alphaB-crystallin (Cryab) as an inhibitor of this process. Silencing of Plk2 or PVR blocked NGF-triggered differentiation and Cryab down-regulation, while silencing of Cryab enhanced NGF-induced differentiation. Our results position both Plk2 and PVR upstream of the negative regulator Cryab in the pathway(s) leading to neuronal differentiation triggered by NGF. |
| Databáze: | OpenAIRE |
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