Protein kinase C inhibitors, H7 and calphostin C, inhibit induction of DNA synthesis by cytosolic extracts of exponentially growing neuroblastoma cells in isolated nuclei.
Cytoplasmic extracts from proliferating Neuro-2a cells contain a protein factor, ADR (activator of DNA replication) that induces DNA synthesis in isolated quiescent nuclei. Cytoplasmic extracts derived from quiescent-made Neuro-2a cells contain none or very little ADR activity, but this activity can be generated after a brief exposure of cytosolic extracts to a membrane-enriched fraction derived from exponentially growing Neuro-2a cells. ADR activity appears at the beginning of the S phase of the cell cycle. Moreover it appears to be a protease, because aprotinin inhibits ADR activity. ADR activity can be also inhibited by the protein kinase C inhibitors, 1-(5-isoquinoline-sulfonyl)-2- methylpiperazine (H7) and calphostin C.
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Instituto de Investigaciones Citológicas de la Fundación Valenciana de Investigaciones Biomédicas, Valencia, Spain.
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D003600:Cytosol / Q000201:enzymology; D004261:DNA Replication / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology*; D051379:Mice; D009281:Naphthalenes; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D007546:Isoquinolines; D009281:Naphthalenes; D010879:Piperazines; D011083:Polycyclic Compounds; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D012697:Serine Endopeptidases; C067404:activator of DNA replication; C058819:calphostin C