Expression of the SRF gene occurs through a Ras/Sp/SRF-mediated-mechanism in response to serum growth signals

Spencer, Jeffrey A.; Misra, Ravi

doi:10.1038/sj.onc.1203121

Cited by 40 publications

(32 citation statements)

References 40 publications

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“…19 However, maximal serum responsiveness requires the presence of the Sp1 binding site immediately adjacent to one of the three CArG elements. 22 The Egr1 promoter contains several potential Sp1 binding sites, one of which is located between two IR-responsive CArG elements. Nevertheless, the placing of an Sp1 binding site in the E6 synthetic promoter (using the identical spacing and sequence context seen in the SRF promoter) did not yield an increase in IR-response.…”

Section: Discussionmentioning

confidence: 99%

“…21 Furthermore, self-regulation of SRF expression via CArG elements in the SRF gene promoter was enhanced by the presence of a binding site for the Sp1 transcription factor. 22 In the present study, CArG numbers, core sequences, spacing and context were specifically altered in an attempt to increase enhancer sensitivity to low doses of ionizing radiation and define parameters important for future promoter development. Lastly, in vitro and in vivo GDEPT assays were used to demonstrate the efficacy of new generation suicide gene vectors containing the improved promoters.…”

Section: Introductionmentioning

confidence: 99%

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Optimizing radiation-responsive gene promoters for radiogenetic cancer therapy

2002

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Optimizing radiation-responsive gene promoters for radiogenetic cancer therapy

2002

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“…Beyond inducible transcription, evidence for the importance of Sp1 in the regulation of the cell cycle is mounting (reviewed by Black et al 2001). Sp1 phosphorylation is known to be dynamic throughout the cell cycle (Leggett et al 1995, Black et al 1999 and Sp1 can mediate a response to mitogenic signals, such as serum, through Ras-pathway activation (Miltenberger et al 1995, Kumar & Butler 1998, Black et al 1999, Spencer & Misra 1999. Furthermore, it is involved in the regulation of cell cycle proteins, such as multiple cyclindependent kinase inhibitors (Kivinen et al 1999, Pagliucia et al 2000, Wang et al 2000, cyclindependent kinase-2 (Tikoo et al 2000), and cyclin D3 (Wang et al 1999b), and is itself regulated by cyclin activity (Shao & Robbins 1995).…”

Section: Sp1 As a Target Of Signal Transduction Cascadesmentioning

confidence: 99%

Role of Sp1 in insulin regulation of gene expression

Samson

Wong²

2002

Journal of Molecular Endocrinology

142

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Sp1 is a ubiquitous nuclear factor that plays a key role in maintaining basal transcription of 'house-keeping' genes. However, recent evidence points to a more important function for Sp1 in mediating 'cross-talk' between selected signaling cascades to regulate the target genes that respond to these pathways. The role of Sp1 in mediating the actions of the peptide hormone insulin is of specific interest and serves as a model for detailing effects of intracellular signaling on Sp1 activity. This review summarizes studies suggesting that changes in Sp1 phosphorylation provide one potential mechanism for manipulating activity of this protein. A growing body of evidence reveals that the DNA binding and transcription activity of Sp1 may increase or decrease in response to changes in phosphorylation. This enables 'fine-tuning' of Sp1 activity for regulation of gene transcription. Several mechanisms exist by which Sp1 alters gene activity in response to insulin. These include independent Sp1 activity as well as collaboration or competition with others factors. This review points to an ever-increasing role for Sp1 in regulating the transcription of genes in response to extracellular signals such as insulin.

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“…1 is a key regulator of many extracellular signal-regulated genes important for cell growth and differentiation (1)(2)(3). SRF was first identified as a critical transcription factor involved in mediating serum-induced transcriptional activation of the c-fos gene (4,5).…”

Section: Serum Response Factor (Srf)mentioning

confidence: 99%

Early Postnatal Cardiac Changes and Premature Death in Transgenic Mice Overexpressing a Mutant Form of Serum Response Factor

Zhang¹,

Chai²,

Azhar³

et al. 2001

Journal of Biological Chemistry

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Serum response factor (SRF) is a key regulator of a number of extracellular signal-regulated genes important for cell growth and differentiation. A form of the SRF gene with a double mutation (dmSRF) was generated. This mutation reduced the binding activity of SRF protein to the serum response element and reduced the capability of SRF to activate the atrial natriuretic factor promoter that contains the serum response element. Cardiac-specific overexpression of dmSRF attenuated the total SRF binding activity and resulted in remarkable morphologic changes in the heart of the transgenic mice. These mice had dilated atrial and ventricular chambers, and their ventricular wall thicknesses were only 1 ⁄2 to 1 ⁄3 the thickness of that of nontransgenic mice. Also these mice had smaller cardiac myocytes and had less myofibrils in their myocytes relative to nontransgenic mice. Altered gene expression and slight interstitial fibrosis were observed in the myocardium of the transgenic mice. All the transgenic mice died within the first 12 days after birth, because of the early onset of severe, dilated cardiomyopathy. These results indicate that dmSRF overexpression in the heart apparently alters cardiac gene expression and blocks normal postnatal cardiac growth and development.

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Expression of the SRF gene occurs through a Ras/Sp/SRF-mediated-mechanism in response to serum growth signals

Cited by 40 publications

References 40 publications

Optimizing radiation-responsive gene promoters for radiogenetic cancer therapy

Optimizing radiation-responsive gene promoters for radiogenetic cancer therapy

Role of Sp1 in insulin regulation of gene expression

Early Postnatal Cardiac Changes and Premature Death in Transgenic Mice Overexpressing a Mutant Form of Serum Response Factor

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