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.

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 Immediate Early Gene Expression in PC12 Cells Exposed to Lead: Requirement for Protein Kinase C

2000 ◽  
Vol 74 (3) ◽  
pp. 1140-1146 ◽  
Author(s):  
Kyung-Ah Kim ◽  
Tamal Chakraborti ◽  
Gary W. Goldstein ◽  
Joseph P. Bressler
Keyword(s):  
Gene Expression ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Pc12 Cells ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Early Gene Expression ◽  
Kinase C

scholarly journals Serum Response Factor Regulates Immediate Early Host Gene Expression in Toxoplasma gondii-Infected Host Cells

PLoS ONE ◽  
2011 ◽  
Vol 6 (3) ◽  
pp. e18335 ◽  
Author(s):  
Mandi Wiley ◽  
Crystal Teygong ◽  
Eric Phelps ◽  
Jay Radke ◽  
Ira J. Blader
Keyword(s):  
Gene Expression ◽  
Toxoplasma Gondii ◽  
Serum Response Factor ◽  
Host Gene ◽  
Host Cells ◽  
Immediate Early ◽  
Infected Host ◽  
Response Factor ◽  
Host Gene Expression ◽  
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.

In vivo carbon monoxide exposure and hypoxic hypoxia stimulate immediate early gene expression

1997 ◽  
Vol 434 (5) ◽  
pp. 568-574 ◽  
Author(s):  
Bernhard Gess ◽  
Konrad Wolf ◽  
Michael Pfeifer ◽  
Günter A. J. Riegger ◽  
A. Kurtz
Keyword(s):  
Gene Expression ◽  
Carbon Monoxide ◽  
Immediate Early Gene ◽  
Hypoxic Hypoxia ◽  
Early Gene ◽  
Immediate Early ◽  
Early 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.

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