Plasminogen Activator Inhibitor Type 2 Contains mRNA Instability Elements within Exon 4 of the Coding Region

Tierney, Marcus; Medcalf, Robert L.

doi:10.1074/jbc.m010627200

Cited by 61 publications

(47 citation statements)

References 45 publications

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“…The analyses of the chimeric mRNAs identified the cis-element in the region corresponding to the ORF. There have been several reports that showed the determinants for mRNA stability in the coding region (45)(46)(47).…”

Section: Fig 7 Ib-mrna Was Stabilized In Response To Lps or Il-1␤ Bmentioning

confidence: 99%

Stimulus-specific Induction of a Novel Nuclear Factor-κB Regulator, IκB-ζ, via Toll/Interleukin-1 Receptor Is Mediated by mRNA Stabilization

Yamazaki

Muta

Matsuo

et al. 2005

Journal of Biological Chemistry

124

131

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We have recently identified an inducible nuclear factor-B (NF-B) regulator, IB-, which is induced by microbial ligands for Toll-like receptors such as lipopolysaccharide and the proinflammatory cytokine interleukin (IL)-1␤ but not by tumor necrosis factor (TNF)-␣. In the present study, we examined mechanisms for stimulus-specific induction of IB-. The analysis of the IB-promoter revealed an essential role for an NF-B binding sequence in transcriptional activation. The activation, however, did not account for the Toll-like receptor/IL-1 receptor-specific induction of IB-, because the promoter analysis and nuclear run-on analysis indicated that its transcription was similarly induced by TNF-␣. To examine post-transcriptional regulation, we analyzed the decay of IB-mRNA, and we found that it was specifically stabilized by lipopolysaccharide or IL-1␤ but not by TNF-␣. Furthermore, we found that costimulation with TNF-␣ and another proinflammatory cytokine, IL-17, elicited the IB-induction. Stimulation with IL-17 alone did not induce IB-but stabilized its mRNA. Therefore, IB-induction requires both NF-B activation and stimulus-specific stabilization of its mRNA. Because IB-is essential for expression of a subset of NF-B target genes, the stimulus-specific induction of IB-may be of great significance in regulation of inflammatory reactions.

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Section: Fig 7 Ib-mrna Was Stabilized In Response To Lps or Il-1␤ Bmentioning

confidence: 99%

Stimulus-specific Induction of a Novel Nuclear Factor-κB Regulator, IκB-ζ, via Toll/Interleukin-1 Receptor Is Mediated by mRNA Stabilization

Yamazaki

Muta

Matsuo

et al. 2005

Journal of Biological Chemistry

124

131

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“…Our previous REMSA studies using HT-1080 cells have shown that a number of cellular factors recognize the PAI-2 AU-rich element and during PMAϩTNF treatment a transient increase in the binding activity of one particular mRNAbinding protein is observed (34). The time course of this transient increase in binding activity parallels the accumulation of TTP mRNA in the same cells (data not shown) raising the possibility that the transiently induced PAI-2 mRNA-binding protein is TTP itself.…”

Section: Ttp Expression Correlates With Reduced Levels Of Pai-2mentioning

confidence: 79%

“…The TTP mammalian expression plasmid CMV.hTTPtag (31) (hereafter referred to as pTTP-HA) was provided by Dr. Paul Bohjanen (University of Minnesota). The wild-type PAI-2 expression plasmid pCI-PAI-2 contains the 1872-bp PAI-2 cDNA (9) inserted into the EcoR1 site of the expression plasmid pCl-neo (Promega, Madison, WI) (34).…”

Section: Methodsmentioning

confidence: 99%

“…Western Blotting-Western blotting was performed as previously described (34). Cytoplasmic extracts (up to 50 g) prepared from cells were separated by SDS-PAGE under reducing conditions and transferred to nylon membranes.…”

Section: Methodsmentioning

confidence: 99%

“…Two functional mRNA instability elements have been identified within the PAI-2 transcript, one within the 3Ј-UTR of PAI-2 mRNA (16,17), and the other within exon 4 of the coding region (34). Closer analysis of the 3Ј-UTR region of PAI-2 mRNA led to the identification of a nonameric AU-rich element (UUAUUUAUU) (ARE), 304-nt upstream from the poly(A) tail, as a mRNA destabilizing determinant (16).…”

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confidence: 99%

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Inherent Instability of Plasminogen Activator Inhibitor Type 2 mRNA Is Regulated by Tristetraprolin

Stasinopoulos

Leedman³

et al. 2003

Journal of Biological Chemistry

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Plasminogen activator inhibitor type 2 (PAI-2) is a serine protease inhibitor that is subject to regulation at the post-transcriptional level. At least two mRNA instability elements reside within the PAI-2 transcript; one in the coding region and another within the 3-untranslated region (UTR). For the latter, a functional AU-rich motif (ARE) has been identified that provides a binding site for a number of cellular proteins, including the mRNA stability protein, HuR. In this study, we used the yeast three-hybrid system to screen a human leukocyte cDNA library to identify other proteins that associate with the PAI-2 ARE. This screen identified tristetraprolin (TTP) as a PAI-2 mRNA ARE-binding protein. UV cross-linking and immunoprecipitation experiments showed that TTP expressed in HEK293 cells could associate with the PAI-2 ARE in vitro. Co-transfection of plasmids expressing TTP and PAI-2 in HEK293 cells resulted in an increase in the decay rate of PAI-2 mRNA and loss of PAI-2 protein in a process that was dependent upon the PAI-2 3-UTR. The 29-nt PAI-2 AU-rich element alone was also capable of conferring TTP-dependent mRNA instability to a reporter transcript. The extent of PAI-2 mRNA stability was remarkably sensitive to TTP since TTP-dependent PAI-2 mRNA decay occurred at TTP levels that were below Western blot detection limits. This study identifies TTP as a functional PAI-2 ARE-binding protein that modulates the post-transcriptional regulation of the PAI-2 gene.

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Plasminogen Activators and Their Inhibitors in Cancer

Leupold

Allgayer

2012

Matrix Proteases in Health and Disease

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Plasminogen Activator Inhibitor Type 2 Contains mRNA Instability Elements within Exon 4 of the Coding Region

Abstract: Plasminogen activator inhibitor type 2 (PAI-2

Cited by 61 publications

References 45 publications

Stimulus-specific Induction of a Novel Nuclear Factor-κB Regulator, IκB-ζ, via Toll/Interleukin-1 Receptor Is Mediated by mRNA Stabilization

Stimulus-specific Induction of a Novel Nuclear Factor-κB Regulator, IκB-ζ, via Toll/Interleukin-1 Receptor Is Mediated by mRNA Stabilization

Inherent Instability of Plasminogen Activator Inhibitor Type 2 mRNA Is Regulated by Tristetraprolin

Plasminogen Activators and Their Inhibitors in Cancer

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