Abstract
The cyclic adenosine monophosphate (AMP) response element-binding protein, CREB, often modulates stress responses. Here, we report that CREB suppresses the glioblastoma proliferative effect of the stress-induced acetylcholinesterase variant, AChE-R. In human U87MG glioblastoma cells, AChE-R formed a triple complex with protein kinase C (PKC) epsilon and the scaffold protein RACK1, enhanced PKCepsilon phosphorylation, and facilitated BrdU incorporation. Either overexpressed CREB, or antisense destruction of AChE-R mRNA, PKC, or protein kinase A (PKA) inhibitors-but not CREB combined with PKC inhibition suppressed-this proliferation, suggesting that CREB's repression of this process involves a PKC-mediated pathway, whereas impaired CREB regulation allows AChE-R-induced, PKA-mediated proliferation of glioblastoma tumors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholinesterase / genetics
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Acetylcholinesterase / metabolism*
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Cell Line, Tumor
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Cell Proliferation
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Cyclic AMP Response Element-Binding Protein
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / metabolism
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GTP-Binding Proteins
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Glioblastoma / metabolism*
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Glioblastoma / pathology*
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Humans
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Multiprotein Complexes / metabolism
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Neoplasm Proteins / metabolism
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Oligonucleotides, Antisense / pharmacology
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Phosphorylation
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Protein Binding
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism
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Protein Kinase C-epsilon
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Receptors for Activated C Kinase
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Receptors, Cell Surface
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transfection
Substances
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CREB1 protein, human
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Cyclic AMP Response Element-Binding Protein
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Multiprotein Complexes
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Neoplasm Proteins
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Oligonucleotides, Antisense
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RACK1 protein, human
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Receptors for Activated C Kinase
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Receptors, Cell Surface
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Transcription Factors
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Cyclic AMP-Dependent Protein Kinases
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PRKCE protein, human
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Protein Kinase C
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Protein Kinase C-epsilon
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Acetylcholinesterase
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GTP-Binding Proteins