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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
2009-11-9
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
13
pubmed:volume
284
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
32053-65
pubmed:dateRevised
2010-11-22
pubmed:meshHeading
pubmed-meshheading:19700763-Animals, pubmed-meshheading:19700763-Blotting, Western, pubmed-meshheading:19700763-Cell Differentiation, pubmed-meshheading:19700763-Cells, Cultured, pubmed-meshheading:19700763-Computational Biology, pubmed-meshheading:19700763-Gene Expression Profiling, pubmed-meshheading:19700763-Genome, pubmed-meshheading:19700763-Humans, pubmed-meshheading:19700763-Mice, pubmed-meshheading:19700763-Nerve Growth Factor, pubmed-meshheading:19700763-Neurons, pubmed-meshheading:19700763-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:19700763-Protein-Serine-Threonine Kinases, pubmed-meshheading:19700763-RNA, Messenger, pubmed-meshheading:19700763-Rats, pubmed-meshheading:19700763-Receptors, Virus, pubmed-meshheading:19700763-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19700763-alpha-Crystallin B Chain
pubmed:year
2009
pubmed:articleTitle
Functional whole-genome analysis identifies Polo-like kinase 2 and poliovirus receptor as essential for neuronal differentiation upstream of the negative regulator alphaB-crystallin.
pubmed:affiliation
Departments of Target Research, Merck Serono International S.A. 9, Chemin de Mines, 1202 Geneva, Switzerland.
pubmed:publicationType
Journal Article