Post-transcriptional regulation of plasminogen activator inhibitor type-1 expression in human pleural mesothelial cells.

Post-transcriptional regulation of plasminogen activator inhibitor type-1 expression in human pleural mesothelial cells.
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人胸膜间皮细胞中纤溶酶原激活剂抑制剂 1 型表达的转录后调节。

DOI:
10.1165/rcmb.2009-0046oc
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发表时间:
2010
影响因子:
6.4
通讯作者:
Idell,Steven
Idell,Steven
中科院分区:
医学1区
文献类型:
--
作者:
Shetty,Sreerama;Velusamy,Thirunavukkarasu;Shetty,RashmiS;Marudamuthu,AmarnathS;Shetty,ShwethaK;Florova,Galina;Tucker,Torry;Koenig,Kathy;Shetty,Praveenkumar;Bhandary,YashodharP;Idell,Steven

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The plasminogen activator inhibitor type–1 (PAI-1) effectively blocks the activities of free and receptor-bound urokinase-type plasminogen activator. Incubation of cultured human pleural mesothelial (Met5A) cells with TGF-β increased PAI-1 protein. TGF-β, phorbol myristate acetate, and the translation inhibitor cycloheximide induced PAI-1 mRNA and slowed its degradation, suggesting that PAI-1 mRNA could be regulated by interaction of a PAI-1 binding protein (PAI-1 mRNABp) with PAI-1 mRNA. We found that an approximately 60 kD cytoplasmic PAI-1 mRNABp is detectable in cytoplasmic extracts of MeT5A human pleural mesothelial and malignant mesothelioma cells. The PAI-1 mRNABp specifically binds to a 33-nt sequence in the 3′ untranslated region of PAI-1 mRNA. Insertion of this 33-nt sequence destabilizes otherwise stable β-globin mRNA, indicating that the binding sequence accelerates decay of endogenous PAI-1 mRNA. Competitive inhibition by overexpression of the 33-nt binding sequence in MeT5A cells reduced PAI-1 mRNA decay and increased PAI-1 protein and mRNA expression, indicating that the PAI-1 mRNABp destabilizes PAI-1 mRNA by its interaction with the endogenous 33-nt binding sequence. Incubation of Met5A cells with TGF-β attenuated the interaction of the PAI-1 mRNABp with the 33-nt sequence. By conventional and affinity purification, we isolated the PAI-1 mRNABp and confirmed its identity as 6-phospho-d-gluconate-NADP oxidoreductase, which specifically interacts with the full-length and the 33-nt sequence of the PAI-1 mRNA 3′ untranslated region. This newly recognized pathway could influence expression of PAI-1 by mesothelial or mesothelioma cells at the level of mRNA stability in the context of pleural inflammation or malignancy.
在人横纹肌肉瘤细胞中,佛波酯可增加纤溶酶原激活剂抑制剂 1 型蛋白、mRNA 和基因转录。
DOI: 10.1016/s0021-9258(19)37642-2
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