EGF activates TTP expression by activation of ELK-1 and EGR-1 transcription factors

Florkowska, Magdalena; Tymoszuk, Piotr; Balwierz, Aleksandra; Skucha, Anna; Kochan, Jakub; Wawro, Mateusz; Stalińska, Krystyna; Kasza, Aneta

doi:10.1186/1471-2199-13-8

Cited by 20 publications

(16 citation statements)

References 43 publications

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“…Various transcription factors control the transcription of TTP [ 22 , 23 ]. Recently, the role of EGR1 has been highlighted in breast cancer cell model and HDAC inhibitors can induce this transcription factor [ 24 , 25 ]. EGR1 is also associated with an immediate/early gene expression response, consistent with the early induction of TTP observed upon TSA treatment ( Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…Our findings suggest that the epigenetic events leading to TTP upregulation by HDAC inhibition do not occur on the TTP promoter itself, but at a different locus, e.g., a transcription factor(s) that regulates expression of TTP. In this context, EGR1 represents a good candidate based on its ability to increase TTP expression in breast cancer cells [ 24 ] and HDAC inhibitors can induce EGR1 expression [ 25 ]. EGR1 is a Cys2His2 zinc finger transcription factor, which binds GC rich region (5'-GNG TGG GCG-3') [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…Previous work has shown that HDAC inhibitors can reactivate EGR1 in various cell types, leading to decreased cell proliferation and increased cell apoptosis [ 25 , 46 , 47 , 48 ]. Other mechanisms controlling EGR1 include various signaling pathways such as the EGF (Epidermal Growth Factor)/ELK1 (Ets domain containing protein) pathway [ 24 ]. EGR1 can also be regulated on a post-transcriptional level.…”

Section: Discussionmentioning

confidence: 99%

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Histone Deacetylase Inhibitors Activate Tristetraprolin Expression through Induction of Early Growth Response Protein 1 (EGR1) in Colorectal Cancer Cells

et al. 2015

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The RNA-binding protein tristetraprolin (TTP) promotes rapid decay of mRNAs bearing 3' UTR AU-rich elements (ARE). In many cancer types, loss of TTP expression is observed allowing for stabilization of ARE-mRNAs and their pathologic overexpression. Here we demonstrate that histone deacetylase (HDAC) inhibitors (Trichostatin A, SAHA and sodium butyrate) promote TTP expression in colorectal cancer cells (HCA-7, HCT-116, Moser and SW480 cells) and cervix carcinoma cells (HeLa). We found that HDAC inhibitors-induced TTP expression, promote the decay of COX-2 mRNA, and inhibit cancer cell proliferation. HDAC inhibitors were found to promote TTP transcription through activation of the transcription factor Early Growth Response protein 1 (EGR1). Altogether, our findings indicate that loss of TTP in tumors occurs through silencing of EGR1 and suggests a therapeutic approach to rescue TTP expression in colorectal cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Histone Deacetylase Inhibitors Activate Tristetraprolin Expression through Induction of Early Growth Response Protein 1 (EGR1) in Colorectal Cancer Cells

et al. 2015

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“…In Xenopus, the expression pattern of beclin1, at stage 19 is partially similar to the expression of zfp36 with a distinctive speckled pattern along the neural fold (Bowes et al, 2010). Beclin-1 is involved in the activation of the autophagy pathway a process which is accompanied by an increase in ERK signaling (Florkowska et al, 2012;Martinez-Lopez et al, 2013). Because neural tube closure appears as being critically controlled by autophagy and apoptosis (Cecconi et al, 2008) it is therefore possible that zfp36 labelling along the neural folds represent a transient activation of zfp36 expression in cells undergoing apoptosis or autophagy.…”

Section: Origin Of Zfp36-positive Cells and Function In The Fusing Nementioning

confidence: 99%

zfp36 expression delineates both myeloid cells and cells localized to the fusing neural folds in Xenopus tropicalis

2014

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Regulatory RNA binding proteins allow for specific control of gene expression in a very dynamic manner. In mammals ZFP36, formerly known as Tristetraprolin, controls the inflammatory response by binding to an AU-rich element located in the 3' untranslated region of its target mRNAs. The developping embryo relies on a population of primitive macrophages to ensure proper immunity. Although the role of zfp36 in adult immunity has been extensively studied, its expression in the developing immune system has been poorly documented. Here, we have used whole mount in situ hybridization with a 3' UTR specific probe to address the expression of zfp36 in developing Xenopus tropicalis embryos. We have shown that zfp36 is expressed in two distinct cellular populations. First, it is a new marker of primititive myeloid cells, being coexpressed with the myeloid marker mpo. Therefore this early expression may suggest a role for zfp36 in macrophage differentiation and activation. In addition, a second cell population was found to transiently express zfp36, but not mpo, along the fusing neural folds and may correspond to cells undergoing autophagy during neural tube closure. KEY WORDS: RNA binding proteins, Xenopus tropicalis, embryonic immunityZFP36 formerly known as Tristetraprolin (TTP) (Lai et al., 2014) belongs to a family of RNA binding Zinc Fingers containing proteins which is composed of 3 members in humans, ZFP36, ZFP36L1 and ZFP36L2. In Xenopus laevis, a fourth member previously called C3H4 and named Zfp36L4 has been identified (Belloc and Méndez, 2008;De et al., 1999;Tréguer et al., 2013).Functionally, ZFP36 has been shown to regulate post-transcriptionnally the inflammatory response by controling the expression level of inflammatory factors such as TNF-alpha (Carballo et al., 1998) or GM-CSF (Carballo et al., 2000. Mice constitutively deficient for ZFP36, albeit apparently normal at birth develop a debilitating inflammatory response (Taylor et al., 1996). ZFP36 acts through the specific binding to AU-rich element present in the 3'UTR of the targeted mRNAs and triggers their destabilization .Extensive work has been conducted to address the function of ZFP36 in the regulation of inflammatory processes while its expression in the developing immune system has been loosely documented. Xenopus is a useful model system to study the multiple steps of early immune system development (Ciau-Uitz et al., 2010). In Xenopus embryos, primitive hematopoiesis is initiated in a ventral region termed the ventral blood island (VBI) that is the equivalent of the mammalian extraembryonic yolk sac. The Int. J. Dev. Biol. 58: 751-755 (2014) VBI is composed of two areas, the anterior VBI (aVBI) and the posterior VBI (pVBI) that give rises to different cell populations. The aVBI originates from blastomeres C1D1 and comprises an hemangioblast-like population of cells expressing both blood and endothelial cell markers at stage 14. Yet, it has recently been shown that in normal situation the aVBI will only produce blood cells (Myers a...

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“…Inhibitor studies involving inhibition of NF-kB, in the presence of IL-1b and LPS, have shown that TTP mRNA is a direct substrate of the NF-kB signaling pathway (King et al, 2009;Chen et al, 2013). Other signaling pathways include the protein kinase C (PKC) pathway, via transcription factor activating protein 2, which was shown to regulate TTP mRNA in the presence of a phorbol ester (Chen et al, 1998;Tan and Parker, 2003;Jalonen et al, 2007;Leppänen et al, 2008Leppänen et al, , 2010 and the epidermal growth factor pathway, via the transcription factor ETS domain-containing protein ELK-1 (Florkowska et al, 2012).…”

Section: Ttp Function: Multiple Levels Of Regulatory Controlmentioning

confidence: 99%

Tristetraprolin and Its Role in Regulation of Airway Inflammation

Prabhala

Ammit

2014

Mol Pharmacol

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Chronic inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are clinically and socioeconomically important diseases globally. Currently the mainstay of anti-inflammatory therapy in respiratory diseases is corticosteroids. Although corticosteroids have proven clinical efficacy in asthma, many asthmatic inflammatory conditions (e.g., infection, exacerbation, and severe asthma) are not responsive to corticosteroids. Moreover, despite an understanding that COPD progression is driven by inflammation, we currently do not have effective anti-inflammatory strategies to combat this disease. Hence, alternative anti-inflammatory strategies are required. p38 mitogen-activated protein kinase (MAPK) has emerged as an important signaling molecule driving airway inflammation, and pharmacological inhibitors against p38 MAPK may provide potential therapies for chronic respiratory disease. In this review, we discuss some of the recent in vitro and in vivo studies targeting p38 MAPK, but suggest that p38 MAPK inhibitors may prove less effective than originally considered because they may block antiinflammatory molecules along with proinflammatory responses. We propose that an alternative strategy may be to target an antiinflammatory molecule farther downstream of p38 MAPK, i.e., tristetraprolin (TTP). TTP is an mRNA-destabilizing, RNAbinding protein that enhances the decay of mRNAs, including those encoding proteins implicated in chronic respiratory diseases. We suggest that understanding the molecular mechanism of TTP expression and its temporal regulation will guide future development of novel anti-inflammatory pharmacotherapeutic approaches to combat respiratory disease.

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EGF activates TTP expression by activation of ELK-1 and EGR-1 transcription factors

Cited by 20 publications

References 43 publications

Histone Deacetylase Inhibitors Activate Tristetraprolin Expression through Induction of Early Growth Response Protein 1 (EGR1) in Colorectal Cancer Cells

Histone Deacetylase Inhibitors Activate Tristetraprolin Expression through Induction of Early Growth Response Protein 1 (EGR1) in Colorectal Cancer Cells

zfp36 expression delineates both myeloid cells and cells localized to the fusing neural folds in Xenopus tropicalis

Tristetraprolin and Its Role in Regulation of Airway Inflammation

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