Functional Antagonism Between RNA Binding Proteins HuR and CUGBP2 Determines the Fate of COX-2 mRNA Translation

Sureban, Sripathi M.; Murmu, Nabendu; Rodriguez, Pavel; May, Randal; Maheshwari, Reeti; Dieckgraefe, Brian K.; Houchen, Courtney W.; Anant, Shrikant

doi:10.1053/j.gastro.2006.12.031

Cited by 75 publications

(79 citation statements)

References 37 publications

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“…Our in vitro studies strongly indicate that, rather than acting primarily via transcriptional up-regulation, Fgf9 acts at the post-transcriptional level and suggest that the mechanism of this interaction partially involves CUGbp2 protein expression. This protein and others, including HuR and Apobec-1, have been implicated in the regulation of Ptgs2 expression in various tumor cell lines (40,41) and in an in vivo model of irradiation injury (60). Comparing the ability of Fgf9 to increase CUGbp2 protein with its ability to increase Ptgs2 mRNA stabilization suggests that increased CUGbp2 is only a portion of the overall mechanism downstream of Fgf9 involved in Ptgs2 expression.…”

Section: Discussionmentioning

confidence: 99%

“…There must also be more than one target of kinase activity. There are a variety of further mRNA-binding proteins that are probably involved in this cascade, some well researched, such as HuR (41), and others unknown.…”

Section: Discussionmentioning

confidence: 99%

“…5) identified multiple mRNA-binding proteins that were preferentially expressed in cMSCs compared with bmMSCs. One of these was CUGbp2, a protein known to stabilize Ptgs2 mRNA (40,41) and whose activity can be regulated by phosphorylation downstream of growth factors (42). We evaluated this gene at both the mRNA and protein level in the context of ERK inhibition and found that although CUGbp2 mRNA was not significantly altered by either serum starvation or by ERK inhibition (Fig.…”

Section: Fgf9 Is Sufficient To Maintain High Levels Of Ptgs2 Expressimentioning

confidence: 99%

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Growth Factor Regulation of Prostaglandin-Endoperoxide Synthase 2 (Ptgs2) Expression in Colonic Mesenchymal Stem Cells

Walker

Brown

Riehl

et al. 2010

Journal of Biological Chemistry

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We previously found that a population of colonic stromal cells that constitutively express high levels of prostaglandin-endoperoxide synthase 2 (Ptgs2, also known as Cox-2) altered their location in the lamina propria in response to injury in a Myd88-dependent manner (Brown, S. L., Riehl, T. E., Walker, M. R., Geske, M. J., Doherty, J. M., Stenson, W. F., and Stappenbeck, T. S. (2007) J. Clin. Invest. 117, 258 -269). At the time of this study, the identity of these cells and the mechanism by which they expressed high levels of Ptgs2 were unknown. Here we found that these colonic stromal cells were mesenchymal stem cells (MSCs). These colonic MSCs expressed high Ptgs2 levels not through interaction with bacterial products but instead as a consequence of mRNA stabilization downstream of Fgf9 (fibroblast growth factor 9), a growth factor that is constitutively expressed by the intestinal epithelium. This stabilization was mediated partially through a mechanism involving endogenous CUG-binding protein 2 (CUGbp2). These studies suggest that Fgf9 is an important factor in the regulation of Ptgs2 in colonic MSCs and may be a factor involved in its constitutive expression in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Fgf9 Is Sufficient To Maintain High Levels Of Ptgs2 Expressimentioning

confidence: 99%

See 1 more Smart Citation

Growth Factor Regulation of Prostaglandin-Endoperoxide Synthase 2 (Ptgs2) Expression in Colonic Mesenchymal Stem Cells

Walker

Brown

Riehl

et al. 2010

Journal of Biological Chemistry

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“…RNA was isolated and subjected to RT-PCR for COX-2, IL-8 and VEGF. In vitro protein interaction studies were performed as reported earlier with recombinant GST-HuR or GST-RBM3 (Sureban et al, 2007).…”

Section: Recombinant Proteinsmentioning

confidence: 99%

“…Luciferase reporter gene assay Luciferase reporter assay was performed with plasmid encoding RBM3 and HuR as described earlier (Sureban et al, 2007).…”

Section: Immunocytochemistrymentioning

confidence: 99%

Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe

et al. 2008

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RNA-binding proteins play a key role in post-transcriptional regulation of mRNA stability and translation. We have identified that RBM3, a translation regulatory protein, is significantly upregulated in human tumors, including a stage-dependent increase in colorectal tumors. Forced RBM3 overexpression in NIH3T3 mouse fibroblasts and SW480 human colon epithelial cells increases cell proliferation and development of compact multicellular spheroids in soft agar suggesting the ability to induce anchorage-independent growth. In contrast, downregulating RBM3 in HCT116 colon cancer cells with specific siRNA decreases cell growth in culture, which was partially overcome when treated with prostaglandin E 2 , a product of cyclooxygenase (COX)-2 enzyme activity. Knockdown also resulted in the growth arrest of tumor xenografts. We have also identified that RBM3 knockdown increases caspase-mediated apoptosis coupled with nuclear cyclin B1, and phosphorylated Cdc25c, Chk1 and Chk2 kinases, implying that under conditions of RBM3 downregulation, cells undergo mitotic catastrophe. RBM3 enhances COX-2, IL-8 and VEGF mRNA stability and translation. Conversely, RBM3 knockdown results in loss in the translation of these transcripts. These data demonstrate that the RNA stabilizing and translation regulatory protein RBM3 is a novel proto-oncogene that induces transformation when overexpressed and is essential for cells to progress through mitosis.

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RNA Regulation in Apoptosis

Roretz

Gallouzi

2013

Encyclopedia of Molecular Cell Biology and Molecular Medicine

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Functional Antagonism Between RNA Binding Proteins HuR and CUGBP2 Determines the Fate of COX-2 mRNA Translation

Cited by 75 publications

References 37 publications

Growth Factor Regulation of Prostaglandin-Endoperoxide Synthase 2 (Ptgs2) Expression in Colonic Mesenchymal Stem Cells

Growth Factor Regulation of Prostaglandin-Endoperoxide Synthase 2 (Ptgs2) Expression in Colonic Mesenchymal Stem Cells

Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe

RNA Regulation in Apoptosis

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