Downregulation of prohormone convertase-1 by a phorbol ester.
Acute TPA treatment (1h, 100nM) of a human pancreatic carcinoid cell line (BON) depletes cell contents of chromogranin A (CGA) and pancreastatin (PST), a peptide derived posttranslationally from CGA. Despite removal of TPA, BON cells continue to release CGA in an unregulated fashion whereas PST secretion is reduced substantially. TPA treatment also reduced prohormone convertase-1 (PC-1) protein and increased PC-1 mRNA levels. Together, these findings indicate that the TPA-induced switch from a regulated to unregulated pattern of CGA secretion is accompanied by a decrease in the processing of CGA to PST and a decrease in the active form of a processing enzyme potentially involved in processing CGA to a smaller peptide, PST.
Udupi
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Department of Surgery, University of Texas Medical Branch, Galveston 77555, USA.
Townsend
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CM
Gomez
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Zhang
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T
Greeley
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GH
D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D002276:Carcinoid Tumor / Q000378:metabolism*; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D010187:Pancreatic Hormones / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D043484:Proprotein Convertases; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D053379:Chromogranin A; D002864:Chromogranins; D010187:Pancreatic Hormones; D012333:RNA, Messenger; C050836:pancreastatin; D043484:Proprotein Convertases; D016282:Aspartic Acid Endopeptidases; D013755:Tetradecanoylphorbol Acetate