Differential Usage of Signal Transduction Pathways Defines Two Types of Serum Response Factor Target Gene

Gineitis, Dziugas; Treisman, Richard

doi:10.1074/jbc.m102678200

Cited by 178 publications

(183 citation statements)

References 59 publications

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“…In cardiomyocytes and in Swiss 3T3 fibroblasts, cytochalasin D was shown to activate RhoA (16,36). Inhibition of RhoA signaling via Rho-associated kinase by 10 M Y27632 partially inhibited cytochalasin D-mediated CTGF induction, 2 but did not reach (37); however, the availability of Gactin as modulator of gene expression seems to be different upon treatment with both agents; cytochalasin D was shown to sequester and thus reduce the effective level of G-actin, thereby activating a subset of genes regulated by serum response factor (38,39). The published promoter sequence of CTGF does not contain a serum response element, and thus far, CTGF transcription has not been characterized as being dependent on activation by serum response factor, suggesting a different molecular mechanism of cytochalasin D action.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the Expression of Connective Tissue Growth Factor by Alterations of the Cytoskeleton

Ott

Iwanciw

Graneß

et al. 2003

Journal of Biological Chemistry

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Modulation of the cytoskeletal architecture was shown to regulate the expression of CTGF (connective tissue growth factor, CCN2). The microtubule disrupting agents nocodazole and colchicine strongly up-regulated CTGF expression, which was prevented upon stabilization of the microtubules by paclitaxel. As a consequence of microtubule disruption, RhoA was activated and the actin stress fibers were stabilized. Both effects were related to CTGF induction. Overexpression of constitutively active RhoA induced CTGF synthesis. Interference with RhoA signaling by simvastatin, toxinB, C3 toxin, and Y27632 prevented up-regulation of CTGF. Likewise, direct disintegration of the actin cytoskeleton by latrunculin B interfered with nocodazolemediated up-regulation of CTGF expression. Disassembly of actin fibers by cytochalasin D, however, unexpectedly increased CTGF expression indicating that the content of F-actin per se was not the major determinant for CTGF gene expression. Given the fact that cytochalasin D sequesters G-actin, a decrease in G-actin increased CTGF, while increased levels of Gactin corresponded to reduced CTGF expression. These data link alterations in the microtubule and actin cytoskeleton to the expression of CTGF and provide a molecular basis for the observation that CTGF is up-regulated in cells exposed to mechanical stress.

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Section: Discussionmentioning

confidence: 99%

Modulation of the Expression of Connective Tissue Growth Factor by Alterations of the Cytoskeleton

Ott

Iwanciw

Graneß

et al. 2003

Journal of Biological Chemistry

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“…egr-1 promoter deletion analyses and gel shift assays identified a cis-activating element (nucleotides À376 to À350) binding to the transcription factor Elk-1 (Chen et al, 2004). Expression of egr-1 is induced by the ternary complex factor Elk-1, which is phosphorylated and activated by ERK1/2 (Janknecht et al, 1993;Gineitis and Treisman, 2001;Andrade et al, 2004). Once phosphorylated by ERK, activated Elk-1 interacts with SRF to bind jointly to SRE in egr-1 promoter, leading to a rapid transcriptional response to various extracellular stimuli (McMahon and Monroe, 1995;Cohen et al, 1996;Watson et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1

2005

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High expression of epidermal growth factor receptor (EGFR) is found in a variety of solid tumors, including colorectal cancer. EGFR has been identified as a rational target for anticancer therapy. Curcumin, the yellow pigment of turmeric in curry, has received attention as a promising dietary supplement for cancer prevention and treatment. We recently reported that curcumin inhibited the growth of human colon cancer-derived Moser cells by suppressing gene expression of cyclinD1 and EGFR. The aim of the present study was to explore the molecular mechanisms underlying curcumin inhibition of gene expression of EGFR in colon cancer cells. The generality of the inhibitory effect of curcumin on gene expression of EGFR was verified in other human colon cancer-derived cell lines, including Caco-2 and HT-29 cells. Promoter deletion assays and sitedirected mutageneses identified a binding site for the transcription factor early growth response-1 (Egr-1) in egfr promoter as a putative curcumin response element in regulating the promoter activity of the gene in Moser cells. Electrophoretic mobility shift assays demonstrated that curcumin significantly reduced the DNA-binding activity of the transcription factor Egr-1 to the curcumin response element. In addition, curcumin reduced the trans-activation activity of Egr-1 by suppressing egr-1 gene expression, which required interruption of the ERK signal pathway and reduction of the level of phosphorylation of Elk-1 and its activity. Taken together, our results demonstrated that curcumin inhibited human colon cancer cell growth by suppressing gene expression of EGFR through reducing the trans-activation activity of Egr-1. These results provided novel insights into the mechanisms of curcumin inhibition of colon cancer cell growth and potential therapeutic strategies for treatment of colon cancer.

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“…In mammalian cells, changes in the G-actin pool are responsible for the regulation of a specific subset of SRF target genes through cofactors that bind G-actin and sense G-actin levels (5,32). In this scenario, the binding of hrp65-2 (or 65-2CTS) to actin might regulate interactions between actin and other cofactors with crucial roles in transcription.…”

Section: Discussionmentioning

confidence: 99%

An actin–ribonucleoprotein interaction is involved in transcription by RNA polymerase II

Percipalle

Fomproix

Kylberg

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

129

107

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To determine the function of actin in the cell nucleus, we sought to identify nuclear actin-binding proteins in the dipteran Chironomus tentans using DNase I-affinity chromatography. We identified the RNA-binding protein hrp65 as an actin-binding protein and showed that the C-terminal sequence of the hrp65-2 isoform is able to interact directly with actin in vitro. In vivo crosslinking and coimmunoprecipitation experiments indicated that hrp65 and actin are also associated in the living cell. Moreover, in vivo administration of a competing peptide corresponding to the C-terminal sequence of hrp65-2 disrupted the actin-hrp65-2 interaction and caused a specific and drastic reduction of transcription as judged by puff regression and diminished bromo-UTP incorporation. Our results indicate that an actin-based mechanism is implicated in the transcription of most if not all RNA polymerase II genes and suggest that an actin-hrp65-2 interaction is required to maintain the normal transcriptional activity of the cell. Furthermore, immunoelectron microscopy experiments and nuclear run-on assays suggest that the actin-hrp65-2 complex plays a role in transcription elongation.A ctin and myosin I are present not only in the cytoplasm but also in the cell nucleus (1, 2), where they have been implicated in transcription of protein-coding genes (3-5) and nuclear export (6). Many other cytoskeletal components have also been found in the cell nucleus, and some of them have been tentatively implicated in gene expression (reviewed in ref. 1).Actin has been found associated with (pre)-messenger ribonucleoprotein (pre-mRNP) complexes in a variety of organisms, and we recently revealed that actin is a bona fide component of the Balbiani ring (BR) pre-mRNP particles in the salivary gland cells of the dipteran Chironomus tentans (7). The BR genes code for large secretory proteins that are expressed in the salivary gland cells of C. tentans (reviewed in ref. 8). The BR pre-mRNAs are assembled into large RNP particles, the BR pre-mRNPs, that can be visualized directly by transmission electron microscopy (reviewed in ref. 9). Actin is incorporated cotranscriptionally into the newly synthesized BR pre-mRNPs by binding to a subset of heterogeneous nuclear RNP (hnRNP) proteins such as the hnRNP A1-like protein hrp36 (7). Remarkably, the presence of actin in RNP complexes is not restricted to the BR particles of C. tentans, because actin has also been found associated with certain hnRNP proteins of the A͞B group in mammalian pre-mRNPs (10).The presence of actin in the cell nucleus is well documented, but the precise role of nuclear actin is still not understood. To obtain further insight into the function(s) of nuclear actin, we sought to identify additional proteins of C. tentans that bind to actin in the cell nucleus. Materials and MethodsDetailed descriptions of the materials and methods can be found in Supporting Materials and Methods, which is published as supporting information on the PNAS web site, www.pnas.org.DNase I-Sepharose Pull-Down...

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Differential Usage of Signal Transduction Pathways Defines Two Types of Serum Response Factor Target Gene

Cited by 178 publications

References 59 publications

Modulation of the Expression of Connective Tissue Growth Factor by Alterations of the Cytoskeleton

Modulation of the Expression of Connective Tissue Growth Factor by Alterations of the Cytoskeleton

Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1

An actin–ribonucleoprotein interaction is involved in transcription by RNA polymerase II

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