CREB regulates AChE-R-induced proliferation of human glioblastoma cells.
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.
Perry
Chava
C
Department of Biological Chemistry, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Sklan
Ella H
EH
Soreq
Hermona
H
D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017362:Cyclic AMP Response Element-Binding Protein; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019204:GTP-Binding Proteins; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051744:Protein Kinase C-epsilon; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D017868:Cyclic AMP-Dependent Protein Kinases; C497255:PRKCE protein, human; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D000110:Acetylcholinesterase; D019204:GTP-Binding Proteins