Plasminogen activator inhibitor type-2 is a major protein induced in human fibroblasts and SK-MEL-109 melanoma cells by tumor necrosis factor.
Tumor necrosis factor (TNF) induces the synthesis of two proteins of Mr 42 and 36 kDa in human fibroblasts and SK-MEL-109 melanoma cells. To identify these proteins, a lambda gt10 cDNA library was prepared from the mRNA of TNF-treated SK-MEL-109 cells. By screening this library, we found a cDNA that preferentially hybridized to TNF-induced RNA. Hybrid-selected mRNA was translated into a protein of 42 kDa; cDNA sequence analysis followed by a comparison with other known protein sequences identified this protein with plasminogen activator inhibitor, type-2 (PAI-2). After removal of TNF, PAI-2 mRNA turned over rapidly, with an apparent half-life of approximately 2.5 h. Addition of dexamethasone increased the turnover of this mRNA, suggesting that the level of PAI-2 mRNA could be regulated post-transcriptionally by glucocorticoids. PAI-2 was not secreted, but accumulated in fibroblasts continuously treated with TNF.
Pytel
B A
BA
Department of Biological Sciences, State University of New York, Albany 12222.
Peppel
K
K
Baglioni
C
C
D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009693:Nucleic Acid Hybridization; D015849:Plasminogen Inactivators / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004273:DNA, Neoplasm; D015849:Plasminogen Inactivators; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha