Posttranscriptional regulation of urokinase receptor mRNA: identification of a novel urokinase receptor mRNA binding protein in human mesothelioma cells - PubMed (original) (raw)
Posttranscriptional regulation of urokinase receptor mRNA: identification of a novel urokinase receptor mRNA binding protein in human mesothelioma cells
S Shetty et al. Mol Cell Biol. 1997 Mar.
Abstract
Treatment of human pleural mesothelioma (MS-1) cells with phorbol myristate acetate (PMA) and cycloheximide results in 17- and 10-fold, respectively, increases in steady-state expression of urokinase-type plasminogen activator receptor (uPAR) mRNA. Studies of transcriptional inhibition by actinomycin D showed four- and sixfold extensions of uPAR mRNA half-life in MS-1 cells treated with PMA and cycloheximide, respectively, suggesting that uPAR gene expression involves a posttranscriptional regulatory mechanism. Using gel mobility shift and UV cross-linking assays, we identified a 50-kDa uPAR mRNA binding protein (uPAR mRNABp) that selectively bound to a 51-nucleotide (nt) fragment of mRNA corresponding to the uPAR coding region. We investigated the possibility that this 51-nt protein binding fragment of uPAR mRNA contains regulatory information for message stability. Chimeric beta-globin/uPAR/beta-globin mRNA containing the 51-nt protein binding fragment was able to destabilize otherwise stable beta-globin mRNA. Conversely, a control chimeric beta-globin/uPAR/beta-globin mRNA containing a 51-nt fragment of the uPAR coding region that does not bind uPAR mRNABp was stable under identical conditions. Binding of uPAR mRNABp to uPAR mRNA was abolished after treatment with cycloheximide and rapidly down-regulated by PMA. These data suggest that the 51-nt protein binding fragment of uPAR mRNA may be involved in mRNA turnover as well as in cycloheximide-induced uPAR message stabilization. Our results indicate a novel mechanism of uPAR gene regulation in which cis elements within a 51-nt coding region interact with a uPAR mRNABp to regulate uPAR message stability.
Similar articles
- A urokinase receptor mRNA binding protein-mRNA interaction regulates receptor expression and function in human pleural mesothelioma cells.
Shetty S, Idell S. Shetty S, et al. Arch Biochem Biophys. 1998 Aug 15;356(2):265-79. doi: 10.1006/abbi.1998.0789. Arch Biochem Biophys. 1998. PMID: 9705217 - A urokinase receptor mRNA binding protein from rabbit lung fibroblasts and mesothelial cells.
Shetty S, Idell S. Shetty S, et al. Am J Physiol. 1998 Jun;274(6):L871-82. doi: 10.1152/ajplung.1998.274.6.L871. Am J Physiol. 1998. PMID: 9609725 - Posttranscriptional regulation of urokinase receptor gene expression in human lung carcinoma and mesothelioma cells in vitro.
Shetty S, Idell S. Shetty S, et al. Mol Cell Biochem. 1999 Sep;199(1-2):189-200. doi: 10.1023/a:1006914800447. Mol Cell Biochem. 1999. PMID: 10544967 - Post-transcriptional regulation of plasminogen activator inhibitor type-1 expression in human pleural mesothelial cells.
Shetty S, Velusamy T, Shetty RS, Marudamuthu AS, Shetty SK, Florova G, Tucker T, Koenig K, Shetty P, Bhandary YP, Idell S. Shetty S, et al. Am J Respir Cell Mol Biol. 2010 Sep;43(3):358-67. doi: 10.1165/rcmb.2009-0046OC. Epub 2009 Oct 23. Am J Respir Cell Mol Biol. 2010. PMID: 19855086 Free PMC article. - Endothelium and disordered fibrin turnover in the injured lung: newly recognized pathways.
Idell S. Idell S. Crit Care Med. 2002 May;30(5 Suppl):S274-80. doi: 10.1097/00003246-200205001-00017. Crit Care Med. 2002. PMID: 12004248 Review.
Cited by
- Regulation of mRNA stability contributes to the function of innate lymphoid cells in various diseases.
Deng Y, Shi S, Luo J, Zhang Y, Dong H, Wang X, Zhou J, Wei Z, Li J, Xu C, Xu S, Sun Y, Ni B, Wu Y, Yang D, Han C, Tian Y. Deng Y, et al. Front Immunol. 2023 Jan 26;14:1118483. doi: 10.3389/fimmu.2023.1118483. eCollection 2023. Front Immunol. 2023. PMID: 36776864 Free PMC article. Review. - Modulation of Cellular Function by the Urokinase Receptor Signalling: A Mechanistic View.
Alfano D, Franco P, Stoppelli MP. Alfano D, et al. Front Cell Dev Biol. 2022 Apr 8;10:818616. doi: 10.3389/fcell.2022.818616. eCollection 2022. Front Cell Dev Biol. 2022. PMID: 35493073 Free PMC article. Review. - p53 and miR-34a Feedback Promotes Lung Epithelial Injury and Pulmonary Fibrosis.
Shetty SK, Tiwari N, Marudamuthu AS, Puthusseri B, Bhandary YP, Fu J, Levin J, Idell S, Shetty S. Shetty SK, et al. Am J Pathol. 2017 May;187(5):1016-1034. doi: 10.1016/j.ajpath.2016.12.020. Epub 2017 Mar 6. Am J Pathol. 2017. PMID: 28273432 Free PMC article. - Regulation of urokinase expression at the posttranscription level by lung epithelial cells.
Shetty SK, Marudamuthu AS, Abernathy D, Shetty RS, Shetty P, Fu J, Idell S, Bhandary YP, Ji H, Liu MC, Shetty S. Shetty SK, et al. Biochemistry. 2012 Jan 10;51(1):205-13. doi: 10.1021/bi201293x. Epub 2011 Dec 23. Biochemistry. 2012. PMID: 22166006 Free PMC article. - Regulation of u-PAR gene expression by H2A.Z is modulated by the MEK-ERK/AP-1 pathway.
Chauhan S, Boyd DD. Chauhan S, et al. Nucleic Acids Res. 2012 Jan;40(2):600-13. doi: 10.1093/nar/gkr725. Epub 2011 Sep 21. Nucleic Acids Res. 2012. PMID: 21937508 Free PMC article.
References
- Biochemistry. 1979 Nov 27;18(24):5294-9 - PubMed
- Biochem J. 1995 Aug 15;310 ( Pt 1):345-52 - PubMed
- Cell. 1986 Jun 6;45(5):675-84 - PubMed
- Science. 1986 Jul 18;233(4761):305-12 - PubMed
- Cell. 1986 Aug 29;46(5):659-67 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials