Signal transduction and the Ets family of transcription factors

Yordy, John S.; Muise‐Helmericks, Robin C.

doi:10.1038/sj.onc.1204036

Cited by 288 publications

(213 citation statements)

References 161 publications

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“…It has been well established that their function can be controlled by phosphorylationmediated effects on DNA binding, protein-protein interaction, transcriptional activation, and subcellular localization (reviewed in [Yordy and Muise-Helmericks, 2000]). The best characterized Ets modulators are the mitogen-activated protein kinases (MAPK): Erk, JNK, and p38.…”

Section: Regulation By Signaling and Post-translational Modificationmentioning

confidence: 99%

Ets proteins in biological control and cancer

Hsu

Trojanowska

Watson

2004

J of Cellular Biochemistry

258

202

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The Ets family consists of a large number of evolutionarily conserved transcription factors, many of which have been implicated in tumor progression. Extensive studies on this family of proteins have focused so far mainly on the biochemical properties and cellular functions of individual factors. Since most of the Ets factors can bind to the core consensus DNA sequence GGAA/T in vitro, it has been a challenge to differentiate redundant from specific functions of various Ets proteins in vivo. Recent findings, however, suggest that such apparent redundancy may in fact be a central component of a network of differentially regulated specific Ets factors, resulting in distinct biological and pathological consequences. The programmed "Ets conversion" appears to play a critical role during tumor progression, especially in control of cellular changes during epithelial-mesenchymal transition and metastasis. Coordination of multiple Ets gene functions also mediates interactions between tumor and stromal cells. As such, these new insights may provide a novel view of the Ets gene family as well as a focal point for studying the complex biological control involved in tumor progression. KeywordsEts; transcriptional regulation; ECM; cancer; invasion; metastasis; EMT; epithelium; stroma The Ets family of proteins consists of a large number of evolutionarily conserved transcription factors. There are 25 human and 26 murine Ets family members. Ets factors control specific genes that perform critical roles in diverse processes, including cell proliferation, apoptosis, differentiation, lymphoid cell development, angiogenesis, and invasiveness [Sementchenko and Watson, 2000]. To date, studies in the field have largely focused on individual Ets factors and have indeed yielded valuable, albeit fragmented, information. Recent findings, on the other hand, have suggested that several Ets factors may participate in a coordinated program that modulates cell migration and invasiveness, thus affecting tumor progression toward metastasis. In this review, we will examine the recent progress in Ets biology and provide a forum for discussion on a systemic view of Ets functions. Detailed descriptions of Ets proteins and their functions have been provided in several recent reviews [Watson and Seth, 2000;Watson et al., 2001;Dittmer, 2003;Oikawa and Yamada, 2003].Cancer results from a multi-step series of genetic changes that lead to essential alterations in cell physiology such as loss of growth controls and normal apoptotic response as well as sustained angiogenesis, invasion, and metastasis [Hanahan and Weinberg, 2000]. While it is known that most human tumors are derived from epithelial cells that have undergone multiple genetic alterations [Hanahan and Weinberg, 2000], it is also becoming clear that the alterations

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Section: Regulation By Signaling and Post-translational Modificationmentioning

confidence: 99%

Ets proteins in biological control and cancer

Hsu

Trojanowska

Watson

2004

J of Cellular Biochemistry

258

202

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“…Mitogenic stimuli activate ERK1/2 MAPK signaling pathways, triggering phosphorylation of SRF coregulators, which are ternary complex factors (TCFs) whose members are ELK-1, SAP1, or Net (Gille et al 1992). Phosphorylated TCFs form a ternary complex with SRF on SREs to initiate transcription in some IEGs (Yordy and Muise-Helmericks 2000). In addition to growth stimulation, IEG expression is associated with apoptosis (Muthukkumar et al 1995).…”

Section: Introductionmentioning

confidence: 99%

Iron deficiency upregulates Egr1 expression

Lee

Prywes

et al. 2015

Genes Nutr

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Iron-deficient anemia is a prevalent disease among humans. We searched for genes regulated by iron deficiency and its regulated mechanism. cDNA microarrays were performed using Hepa1c1c7 cells treated with 100 lM desferrioxamine (DFO), an iron chelator. Early growth response 1 (Egr1) was upregulated with at least 20-fold increase within 4 h and lasted for 24 h, which was confirmed by qRT-PCR. This activation was not seen by ferric ammonium citrate (FAC). DFO increased the transcriptional activity of Egr1-luc (-604 to ?160) and serum response element (SRE)-luc reporters by 2.7-folds. In addition, cycloheximide lowered DFO-induced Egr1 mRNA levels. The upregulation of Egr1 by DFO was accompanied by sustained ERK signals along with phosphorylation of Elk-1. The ERK inhibitor (PD98059) prevented the DFO-induced Egr1 mRNAs. Overexpression of Elk-1 mutant (pElk-1S383A) decreased Egr1 reporter activity. DFO lowered reactive oxygen species (ROS) production and increased caspase 3/7 activity and cell death. DFO-induced iron deficiency upregulates Egr1 in part through transcriptional activation via ERK and Elk-1 signals, which may be important in the regulation of cell death in hepatoma cells. Our study demonstrated that iron depletion controlled the expression of Egr1, which might contribute to decisions about cellular fate in response to iron deficiency.

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“…This latter pathway is of particular interest in this study, in that the ERK signaltransduction pathway is activated by EGFR. An important downstream transcription factor target of ERK1/2 is Elk-1, a member of the ets family of transcription factors (Yordy and Muise-Helmericks, 2000). Therefore, we decided to assess the ability of PKC-Z to activate the classic PKC target AP-1, and/or the ERK target, Elk-1.…”

Section: Introductionmentioning

confidence: 99%