Tristetraprolin regulates TNF TNF-α mRNA stability via a proteasome dependent mechanism involving the combined action of the ERK and p38 pathways

Deleault, Kristen M.; Skinner, S.J.M.; Brooks, S. E. H.

doi:10.1016/j.molimm.2007.05.017

Cited by 116 publications

(126 citation statements)

References 59 publications

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“…The mechanism mediating the increase in luciferase expression is unclear. LPS stimulation (100 ng/ml, 90 min) did not alter pGL3-Control luciferase expression in either of the cell lines, consistent with previous findings with pGL3-Control luciferase expression (19,30). Luciferase expression from the pGL3-TNF-39 UTR vector is significantly lower than expression from the pGL3-Control vector, due to the presence of the TNF-a 39 UTR, consistent with our previous findings (30,32).…”

Section: Cul4b Knockdown Inhibits Tnf-a 39 Utr Luciferase Expressionsupporting

confidence: 91%

“…LPS stimulation of the control shRNA cells results in a dramatic increase in TNF-a mRNA levels, peaking at ∼2 h and then beginning to decline (Fig. 3A), consistent with our previous findings (19,30). In contrast, TNF-a mRNA levels are significantly reduced in the Cul4B shRNA cells (p , 0.01 at 1, 2, and 4 h LPS).…”

Section: Cul4b Is Necessary For Tnf-a Mrna Stabilizationsupporting

confidence: 91%

“…Both increases are significant compared with resting TNF-a 39 UTR luciferase expression (p , 0.01) and of a magnitude consistent with our previous findings (19,30). Induction of TNF-a 39 UTR luciferase expression by LPS is lower in the Cul4B shRNA cells compared with the control cells.…”

Section: Cul4b Knockdown Inhibits Tnf-a 39 Utr Luciferase Expressionsupporting

confidence: 90%

“…Following 90 min of LPS stimulation (Fig. 3D), the TNF-a mRNA t 1/2 increases to 68.8 min in control shRNA cells, consistent with our previous findings in RAW24.7 cells (30). In contrast, the TNF-a mRNA t 1/2 in the Cul4B shRNA cells is 33.3 min.…”

Section: Cul4b Is Necessary For Tnf-a Mrna Stabilizationsupporting

confidence: 90%

“…These studies employ pGL3-Control and TNF-39 UTR luciferase reporters, which differ only in the presence of the TNF-a 39 UTR, as well as several TTP expression constructs (5,19,(30)(31)(32)(33). Our hypothesis for these experiments was that TNF-a luciferase expression would be lower in the Cul4B shRNA cells compared with the control shRNA cells.…”

Section: Cul4b Knockdown Inhibits Tnf-a 39 Utr Luciferase Expressionmentioning

confidence: 99%

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Cullin 4B Is Recruited to Tristetraprolin-Containing Messenger Ribonucleoproteins and Regulates TNF-α mRNA Polysome Loading

Pfeiffer

Brooks

2012

The Journal of Immunology

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TNF-α is a central mediator of inflammation and critical for host response to infection and injury. TNF-α biosynthesis is controlled by transcriptional and posttranscriptional mechanisms allowing for rapid, transient production. Tristetraprolin (TTP) is an AU-rich element binding protein that regulates the stability of the TNF-α mRNA. Using a screen to identify TTP-interacting proteins, we identified Cullin 4B (Cul4B), a scaffolding component of the Cullin ring finger ligase family of ubiquitin E3 ligases. Short hairpin RNA knockdown of Cul4B results in a significant reduction in TNF-α protein and mRNA in LPS-stimulated mouse macrophage RAW264.7 cells as well as a reduction in TTP protein. TNF-α message t1/2 was reduced from 69 to 33 min in LPS-stimulated cells. TNF-3′ untranslated region luciferase assays utilizing wild-type and mutant TTP-AA (S52A, S178A) indicate that TTP function is enhanced in Cul4B short hairpin RNA cells. Importantly, the fold induction of TNF-α mRNA polysome loading in response to LPS stimulation is reduced by Cul4B knockdown. Cul4B is present on the polysomes and colocalizes with TTP to exosomes and processing bodies, which are sites of mRNA decay. We conclude that Cul4B licenses the TTP-containing TNF-α messenger ribonucleoprotein for loading onto polysomes, and reduction of Cul4B expression shunts the messenger ribonucleoproteins into the degradative pathway.

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Section: Cul4b Knockdown Inhibits Tnf-a 39 Utr Luciferase Expressionsupporting

confidence: 91%

Section: Cul4b Is Necessary For Tnf-a Mrna Stabilizationsupporting

confidence: 91%

Section: Cul4b Knockdown Inhibits Tnf-a 39 Utr Luciferase Expressionsupporting

confidence: 90%

Section: Cul4b Is Necessary For Tnf-a Mrna Stabilizationsupporting

confidence: 90%

Section: Cul4b Knockdown Inhibits Tnf-a 39 Utr Luciferase Expressionmentioning

confidence: 99%

See 3 more Smart Citations

Cullin 4B Is Recruited to Tristetraprolin-Containing Messenger Ribonucleoproteins and Regulates TNF-α mRNA Polysome Loading

Pfeiffer

Brooks

2012

The Journal of Immunology

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Stimulation of macrophage TNFα production by orthopaedic wear particles requires activation of the ERK1/2/Egr‐1 and NF‐κB pathways but is independent of p38 and JNK

Beidelschies

Huang

McMullen

et al. 2008

Journal Cellular Physiology

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Bone loss that causes aseptic loosening of orthopaedic implants is initiated by pro-inflammatory cytokines produced by macrophages in response to implant-derived wear particles. MAPK and NF-κB signaling pathways are activated by the particles; however, it is not clear which of the signaling pathways are important for the initial response to the wear particles and which are only involved at later steps in the process, such as osteoclast differentiation. Here, we show that the ERK1/2, p38, JNK, and NF-κB pathways are rapidly activated by the wear particles but that only the ERK1/2 and NF-κB pathways are required for the initial response to the wear particles, which include increases in TNFα promoter activity, TNFα mRNA expression, and secretion of TNFα protein. Moreover, ERK1/2 activation by wear particles is also required for increased expression of the transcription factor Egr-1 as well as Egr-1's ability to bind to and activate the TNFα romoter. These results, together with our previous studies of the PI3K/Akt pathway, demonstrate that wear particles coordinately activate multiple signaling pathways and multiple transcription factors to stimulate production of pro-inflammatory cytokines, such as TNFα. The current study also demonstrates that the signaling pathways are activated to a much greater extent by wear particles with adherent endotoxin than by "endotoxin-free" wear particles. These results, together with those demonstrating the requirement for ERK1/2/Egr-1 and NF-κB, show that activation of these signaling pathways is responsible for the ability of adherent endotoxin to potentiate cytokine production, osteoclast differentiation, and bone loss induced by wear particles.

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Cryptotanshinone, a novel tumor angiogenesis inhibitor, destabilizes tumor necrosis factor‐α mRNA via decreasing nuclear–cytoplasmic translocation of RNA‐binding protein HuR

Zhu

Zhao

et al. 2015

Mol. Carcinog.

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Cryptotanshinone (CT), one major lipophilic component isolated from Salvia miltiorrhiza Bunge, has shown to possess chemopreventive properties against various types of cancer cells. In this study, CT was shown to be a potent anti-angiogenic agent in zebrafish, and mouse models and could limit tumor growth by inhibiting tumor angiogenesis. We further found that CT could inhibit the proliferation, migration, angiogenic sprouting, and tube formation of HUVECs. In addition, we demonstrated that CT could lower the level of TNF-α due to the destabilization of TNF-α mRNA, which associated with regulating 3'-untranslated region (3'-UTR) of TNF-α and preventing the translocation of RNA binding protein, HuR, from the nucleus to the cytoplasm. Moreover, the underlying mechanism responsible for the regulation in angiogenesis by CT was partially related to the suppression of NF-κB, and STAT3 activity. Based on the abilities of CT in targeting tumor cells, inhibiting angiogenesis, and destroying tumor vasculature, CT is worthy of further investigation for preventive, and therapeutic purposes in cancer. © 2015 Wiley Periodicals, Inc.

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Tristetraprolin regulates TNF TNF-α mRNA stability via a proteasome dependent mechanism involving the combined action of the ERK and p38 pathways

Cited by 116 publications

References 59 publications

Cullin 4B Is Recruited to Tristetraprolin-Containing Messenger Ribonucleoproteins and Regulates TNF-α mRNA Polysome Loading

Cullin 4B Is Recruited to Tristetraprolin-Containing Messenger Ribonucleoproteins and Regulates TNF-α mRNA Polysome Loading

Stimulation of macrophage TNFα production by orthopaedic wear particles requires activation of the ERK1/2/Egr‐1 and NF‐κB pathways but is independent of p38 and JNK

Cryptotanshinone, a novel tumor angiogenesis inhibitor, destabilizes tumor necrosis factor‐α mRNA via decreasing nuclear–cytoplasmic translocation of RNA‐binding protein HuR

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