scholarly journals Identification of a coactivator that increases activation of transcription by serum response factor and GAL4-VP16 in vitro.

1992 ◽  
Vol 89 (12) ◽  
pp. 5291-5295 ◽  
Author(s):  
H. Zhu ◽  
R. Pyrwes
Keyword(s):  
Serum Response Factor ◽  
Response Factor ◽  
Activation Of Transcription ◽  
Serum Response

scholarly journals Interaction of ATF6 and serum response factor.

1997 ◽  
Vol 17 (9) ◽  
pp. 4957-4966 ◽  
Author(s):  
C Zhu ◽  
F E Johansen ◽  
R Prywes
Keyword(s):  
Reporter Gene ◽  
Transcriptional Activation ◽  
Leucine Zipper ◽  
Serum Response Factor ◽  
Response Factor ◽  
Basic Leucine Zipper ◽  
Transcriptional Activation Domain ◽  
Activation Of Transcription ◽  
Serum Response

Serum response factor (SRF) is a transcription factor which binds to the serum response element (SRE) in the c-fos promoter. It is required for regulated expression of the c-fos gene as well as other immediate-early genes and some tissue-specific genes. To better understand the regulation of SRF, we used a yeast interaction assay to screen a human HeLa cell cDNA library for SRF-interacting proteins. ATF6, a basic-leucine zipper protein, was isolated by binding to SRF and in particular to its transcriptional activation domain. The binding of ATF6 to SRF was also detected in vitro. An ATF6-VP16 chimera activated expression of an SRE reporter gene in HeLa cells, suggesting that ATF6 can interact with endogenous SRF. More strikingly, an antisense ATF6 construct reduced serum induction of a c-fos reporter gene, suggesting that ATF6 is involved in activation of transcription by SRF. ATF6 was previously partially cloned as a member of the ATF family. The complete cDNA of ATF6 was isolated, and its expression pattern was described.

Functional antagonism between YY1 and the serum response factor

1992 ◽  
Vol 12 (9) ◽  
pp. 4209-4214
Author(s):  
A Gualberto ◽  
D LePage ◽  
G Pons ◽  
S L Mader ◽  
K Park ◽  
...  
Keyword(s):  
Serum Response Factor ◽  
Regulatory Element ◽  
Target Sequence ◽  
Response Factor ◽  
Basal Expression ◽  
Actin Promoter ◽  
Alpha Actin ◽  
Serum Response

The rapid, transient induction of the c-fos proto-oncogene by serum growth factors is mediated by the serum response element (SRE). The SRE shares homology with the muscle regulatory element (MRE) of the skeletal alpha-actin promoter. It is not known how these elements respond to proliferative and cell-type-specific signals, but the response appears to involve the binding of the serum response factor (SRF) and other proteins. Here, we report that YY1, a multifunctional transcription factor, binds to SRE and MRE sequences in vitro. The methylation interference footprint of YY1 overlaps with that of the SRF, and YY1 competes with the SRF for binding to these DNA elements. Overexpression of YY1 repressed serum-inducible and basal expression from the c-fos promoter and repressed basal expression from the skeletal alpha-actin promoter. YY1 also repressed expression from the individual SRE and MRE sequences upstream from a TATA element. Unlike that of YY1, SRF overexpression alone did not influence the transcriptional activity of the target sequence, but SRF overexpression could reverse YY1-mediated trans repression. These data suggest that YY1 and the SRF have antagonistic functions in vivo.

MiR-483-5p controls angiogenesis in vitro and targets serum response factor

FEBS Letters ◽  
2011 ◽  
Vol 585 (19) ◽  
pp. 3095-3100 ◽  
Author(s):  
Yu Qiao ◽  
Ning Ma ◽  
Xidi Wang ◽  
Yang Hui ◽  
Fuyuan Li ◽  
...  
Keyword(s):  
Serum Response Factor ◽  
Response Factor ◽  
Serum Response

scholarly journals Cardiac Tissue Enriched Factors Serum Response Factor and GATA-4 Are Mutual Coregulators

2000 ◽  
Vol 20 (20) ◽  
pp. 7550-7558 ◽  
Author(s):  
Narasimhaswamy S. Belaguli ◽  
Jorge L. Sepulveda ◽  
Vishal Nigam ◽  
Frédéric Charron ◽  
Mona Nemer ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Cardiac Tissue ◽  
Serum Response Factor ◽  
Zinc Finger Protein ◽  
Response Factor ◽  
Mads Box ◽  
Cardiovascular Tissue ◽  
Serum Response

ABSTRACT Combinatorial interaction among cardiac tissue-restricted enriched transcription factors may facilitate the expression of cardiac tissue-restricted genes. Here we show that the MADS box factor serum response factor (SRF) cooperates with the zinc finger protein GATA-4 to synergistically activate numerous myogenic and nonmyogenic serum response element (SRE)-dependent promoters in CV1 fibroblasts. In the absence of GATA binding sites, synergistic activation depends on binding of SRF to the proximal CArG box sequence in the cardiac and skeletal α-actin promoter. GATA-4's C-terminal activation domain is obligatory for synergistic coactivation with SRF, and its N-terminal domain and first zinc finger are inhibitory. SRF and GATA-4 physically associate both in vivo and in vitro through their MADS box and the second zinc finger domains as determined by protein A pullout assays and by in vivo one-hybrid transfection assays using Gal4 fusion proteins. Other cardiovascular tissue-restricted GATA factors, such as GATA-5 and GATA-6, were equivalent to GATA-4 in coactivating SRE-dependent targets. Thus, interaction between the MADS box and C4 zinc finger proteins, a novel regulatory paradigm, mediates activation of SRF-dependent gene expression.

scholarly journals Functional antagonism between YY1 and the serum response factor.

1992 ◽  
Vol 12 (9) ◽  
pp. 4209-4214 ◽  
Author(s):  
A Gualberto ◽  
D LePage ◽  
G Pons ◽  
S L Mader ◽  
K Park ◽  
...  
Keyword(s):  
Serum Response Factor ◽  
Regulatory Element ◽  
Target Sequence ◽  
Response Factor ◽  
Basal Expression ◽  
Actin Promoter ◽  
Alpha Actin ◽  
Serum Response

The rapid, transient induction of the c-fos proto-oncogene by serum growth factors is mediated by the serum response element (SRE). The SRE shares homology with the muscle regulatory element (MRE) of the skeletal alpha-actin promoter. It is not known how these elements respond to proliferative and cell-type-specific signals, but the response appears to involve the binding of the serum response factor (SRF) and other proteins. Here, we report that YY1, a multifunctional transcription factor, binds to SRE and MRE sequences in vitro. The methylation interference footprint of YY1 overlaps with that of the SRF, and YY1 competes with the SRF for binding to these DNA elements. Overexpression of YY1 repressed serum-inducible and basal expression from the c-fos promoter and repressed basal expression from the skeletal alpha-actin promoter. YY1 also repressed expression from the individual SRE and MRE sequences upstream from a TATA element. Unlike that of YY1, SRF overexpression alone did not influence the transcriptional activity of the target sequence, but SRF overexpression could reverse YY1-mediated trans repression. These data suggest that YY1 and the SRF have antagonistic functions in vivo.

scholarly journals Inhibition of Serum Response Factor Improves Response to Enzalutamide in Prostate Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3540
Author(s):  
R. William Watson ◽  
Haleema Azam ◽  
Claudia Aura ◽  
Niamh Russell ◽  
Janet McCormack ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Serum Response Factor ◽  
Specific Antigen ◽  
Xenograft Model ◽  
Tumour Volume ◽  
Lead Target ◽  
Response Factor ◽  
Serum Response

Castrate-resistant prostate cancer (CRPC) is challenging to treat with the androgen receptor (AR), the main target and key focus of resistance. Understanding the mechanisms of AR interaction with co-regulators will identify new therapeutic targets to overcome AR resistance mechanisms. We previously identified the serum response factor (SRF) as a lead target in an in vitro model of CRPC and showed that SRF expression in tissues of CRPC patients was associated with shorter survival. Here, we tested SRF inhibition in vitro and in vivo to assess SRF as a potential target in CRPC. Inhibition of SRF with the small-molecule inhibitor CCG1423 resulted in enhanced response to enzalutamide in vitro and reduced tumour volume of LuCaP 35CR, a CRPC patient-derived xenograft model. Nuclear localisation of AR post-CCG1423 was significantly decreased and was associated with decreased α-tubulin acetylation in vitro and decreased prostate specific antigen (PSA) levels in vivo. SRF immunoreactivity was tested in metastatic tissues from CRPC patients to investigate its role in enzalutamide response. Kaplan–Meier curves showed that high SRF expression was associated with shorter response to enzalutamide. Our study supports the use of SRF inhibitors to improve response to enzalutamide.

scholarly journals Protein Kinase Cδ Blocks Immediate-Early Gene Expression in Senescent Cells by Inactivating Serum Response Factor

2004 ◽  
Vol 24 (16) ◽  
pp. 7298-7311 ◽  
Author(s):  
Keith Wheaton ◽  
Karl Riabowol
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Serum Response Factor ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Response Factor ◽  
Serum Response

ABSTRACT Fibroblasts lose the ability to replicate in response to growth factors and become unable to express growth-associated immediate-early genes, including c-fos and egr-1, as they become senescent. The serum response factor (SRF), a major transcriptional activator of immediate-early gene promoters, loses the ability to bind to the serum response element (SRE) and becomes hyperphosphorylated in senescent cells. We identify protein kinase C delta (PKCδ) as the kinase responsible for inactivation of SRF both in vitro and endogenously in senescent cells. This is due to a higher level of PKCδ activity as cells age, production of the PKCδ catalytic fragment, and its nuclear localization in senescent but not in low-passage-number cells. The phosphorylation of T160 of SRF by PKCδ in vitro and in vivo led to loss of SRF DNA binding activity. Both the PKCδ inhibitor rottlerin and ectopic expression of a dominant negative form of PKCδ independently restored SRE-dependent transcription and immediate-early gene expression in senescent cells. Modulation of PKCδ activity in vivo with rottlerin or bistratene A altered senescent- and young-cell morphology, respectively. These observations support the idea that the coordinate transcriptional inhibition of several growth-associated genes by PKCδ contributes to the senescent phenotype.

Loss of Serum Response Factor Activity Is the Basis of Reduced C-FOS Expression in Aging Human Fibroblasts

1996 ◽  
Vol 15 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Peter W. Atadja ◽  
Karl T. Riabowol
Keyword(s):  
Serum Response Factor ◽  
Human Fibroblasts ◽  
Response Factor ◽  
Nous Rapportons ◽  
Factor Activity ◽  
De Se ◽  
Fos Expression ◽  
Serum Response

RÉSUMÉLes fibroblastes diploïdes humains subissent un nombre limité de dédoublements de population in vitro et sont largement utilisés comme modèle de vieillissement cellulaire. Malgré l'évidence grandissante que le vieillissement cellulaire est dû à une modification de l'expression du gène, l'activité des facteurs de transcription des cellules âgées est encore mal connue. Ici, nous rapportons que la réduction dramatique de l'expression du facteur de transcription fos durant le vieillissement cellulaire semble due à l'incapacité d'un autre facteur de transcription, le facteur réponse de sérum (FRS), de se lier à son site de reconnaissance appelé élément de réponse du sérum (ERS). Ce site est situé en amont de plusieurs gènes comprenant le gène humain c-fos. À l'opposé, les activités des protéines liées à la boîte TATA de la polymérase ARN ainsi qu'à l'élément réponse AMPc sont conservées chez les fibroblastes humains vieillissants. Nous présentons l'évidence que l'hyperphosphorilation du FRS induit une baisse du pouvoir de liaison observée au cours des dernières divisions cellulaires comme ceci a été précédemment suggéré pour la protéine fos.

scholarly journals Serum Response Factor (SRF) Drives the Transcriptional Upregulation of the MDM4 Oncogene in HCC

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 199
Author(s):  
Rossella Pellegrino ◽  
Abhishek Thavamani ◽  
Diego F. Calvisi ◽  
Jan Budczies ◽  
Ariane Neumann ◽  
...  
Keyword(s):  
Copy Number ◽  
Molecular Mechanisms ◽  
Serum Response Factor ◽  
Liver Tumors ◽  
Luciferase Reporter ◽  
Precision Oncology ◽  
Response Factor ◽  
Murine Liver ◽  
Serum Response

Different molecular mechanisms support the overexpression of the mouse double minute homolog 4 (MDM4), a functional p53 inhibitor, in human hepatocellular carcinoma (HCC). However, the transcription factors (TFs) leading to its transcriptional upregulation remain unknown. Following promoter and gene expression analyses, putative TFs were investigated using gene-specific siRNAs, cDNAs, luciferase reporter assays, chromatin immunoprecipitation, and XI-011 drug treatment in vitro. Additionally, MDM4 expression was investigated in SRF-VP16iHep transgenic mice. We observed a copy-number-independent upregulation of MDM4 in human HCCs. Serum response factor (SRF), ELK1 and ELK4 were identified as TFs activating MDM4 transcription. While SRF was constitutively detected in TF complexes at the MDM4 promoter, presence of ELK1 and ELK4 was cell-type dependent. Furthermore, MDM4 was upregulated in SRF-VP16-driven murine liver tumors. The pharmacological inhibitor XI-011 exhibited anti-MDM4 activity by downregulating the TFs driving MDM4 transcription, which decreased HCC cell viability and increased apoptosis. In conclusion, SRF drives transcriptional MDM4 upregulation in HCC, acting in concert with either ELK1 or ELK4. The transcriptional regulation of MDM4 may be a promising target for precision oncology of human HCC, as XI-011 treatment exerts anti-MDM4 activity independent from the MDM4 copy number and the p53 status.

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