scholarly journals Downregulation of DUSP6, a negative regulator of oncogenic ERK signaling, by ACA‐28 induces apoptosis in NIH/3T3 cells overexpressing HER2/ErbB2

2020 ◽  
Author(s):  
Yuki Kanda ◽  
Ayami Mizuno ◽  
Teruaki Takasaki ◽  
Ryosuke Satoh ◽  
Kanako Hagihara ◽  
...  
Keyword(s):  
Negative Regulator ◽  
Erk Signaling ◽  
3T3 Cells ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

scholarly journals Induction of β3-Integrin Gene Expression by Sustained Activation of the Ras-Regulated Raf–MEK–Extracellular Signal-Regulated Kinase Signaling Pathway

2001 ◽  
Vol 21 (9) ◽  
pp. 3192-3205 ◽  
Author(s):  
Douglas Woods ◽  
Holly Cherwinski ◽  
Eleni Venetsanakos ◽  
Arun Bhat ◽  
Stephan Gysin ◽  
...  
Keyword(s):  
Cell Surface ◽  
Signaling Pathway ◽  
Erk Signaling ◽  
Integrin Expression ◽  
3T3 Cells ◽  
Extracellular Signal ◽  
Integrin Gene ◽  
Β3 Integrin ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ABSTRACT Alterations in the expression of integrin receptors for extracellular matrix (ECM) proteins are strongly associated with the acquisition of invasive and/or metastatic properties by human cancer cells. Despite this, comparatively little is known of the biochemical mechanisms that regulate the expression of integrin genes in cells. Here we demonstrate that the Ras-activated Raf–MEK–extracellular signal-regulated kinase (ERK) signaling pathway can specifically control the expression of individual integrin subunits in a variety of human and mouse cell lines. Pharmacological inhibition of MEK1 in a number of human melanoma and pancreatic carcinoma cell lines led to reduced cell surface expression of α6- and β3-integrin. Consistent with this, conditional activation of the Raf-MEK-ERK pathway in NIH 3T3 cells led to a 5 to 20-fold induction of cell surface α6- and β3-integrin expression. Induced β3-integrin was expressed on the cell surface as a heterodimer with αv-integrin; however, the overall level of αv-integrin expression was not altered by Ras or Raf. Raf-induced β3-integrin was observed in primary and established mouse fibroblast lines and in mouse and human endothelial cells. Consistent with previous reports of the ability of the Raf-MEK-ERK signaling pathway to induce β3-integrin gene transcription in human K-562 erythroleukemia cells, Raf activation in NIH 3T3 cells led to elevated β3-integrin mRNA. However, unlike immediate-early Raf targets such as heparin binding epidermal growth factor and Mdm2, β3-integrin mRNA was induced by Raf in a manner that was cycloheximide sensitive. Surprisingly, activation of the Raf-MEK-ERK signaling pathway by growth factors and mitogens had little or no effect on β3-integrin expression, suggesting that the expression of this gene requires sustained activation of this signaling pathway. In addition, despite the robust induction of cell surface αvβ3-integrin expression by Raf in NIH 3T3 cells, such cells display decreased spreading and adhesion, with a loss of focal adhesions and actin stress fibers. These data suggest that oncogene-induced alterations in integrin gene expression may participate in the changes in cell adhesion and migration that accompany the process of oncogenic transformation.

Both products of the fosB gene, FosB and its short form, FosB/SF, are transcriptional activators in fibroblasts

1991 ◽  
Vol 11 (11) ◽  
pp. 5470-5478
Author(s):  
P Dobrazanski ◽  
T Noguchi ◽  
K Kovary ◽  
C A Rizzo ◽  
P S Lazo ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cell Cycle Progression ◽  
Short Form ◽  
Constitutive Expression ◽  
Inhibitory Effect ◽  
Negative Regulator ◽  
3T3 Cells ◽  
C Terminus ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

We demonstrate that a member of the fos family, the fosB gene, gives rise to two transcripts by alternative splicing of exon 4, generating two proteins, FosB of 338 amino acids and a short form, FosB/SF, which contains the DNA binding and dimerization domains but not the 101 amino acids of the C terminus. FosB/SF activates an AP-1-chloramphenicol acetyltransferase construct in NIH 3T3 cells, as determined by transient and stable transfections, although more weakly than does FosB. In contrast to FosB, FosB/SF has lost its ability to repress the dyad symmetry element of the c-fos gene. FosB/SF when expressed in excess to FosB can downmodulate the activity of FosB. Constitutive expression of high levels of FosB/SF in NIH 3T3 cells has no significant inhibitory effect in the induction of cell proliferation or cell cycle progression, indicating that FosB/SF is not a negative regulator of cell growth. This conclusion is further confirmed by the observation that the majority of the Jun molecules are complexed with FosB/SF in the FosB/SF-overexpressing cells.

scholarly journals Both products of the fosB gene, FosB and its short form, FosB/SF, are transcriptional activators in fibroblasts.

1991 ◽  
Vol 11 (11) ◽  
pp. 5470-5478 ◽  
Author(s):  
P Dobrazanski ◽  
T Noguchi ◽  
K Kovary ◽  
C A Rizzo ◽  
P S Lazo ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cell Cycle Progression ◽  
Short Form ◽  
Constitutive Expression ◽  
Inhibitory Effect ◽  
Negative Regulator ◽  
3T3 Cells ◽  
C Terminus ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

We demonstrate that a member of the fos family, the fosB gene, gives rise to two transcripts by alternative splicing of exon 4, generating two proteins, FosB of 338 amino acids and a short form, FosB/SF, which contains the DNA binding and dimerization domains but not the 101 amino acids of the C terminus. FosB/SF activates an AP-1-chloramphenicol acetyltransferase construct in NIH 3T3 cells, as determined by transient and stable transfections, although more weakly than does FosB. In contrast to FosB, FosB/SF has lost its ability to repress the dyad symmetry element of the c-fos gene. FosB/SF when expressed in excess to FosB can downmodulate the activity of FosB. Constitutive expression of high levels of FosB/SF in NIH 3T3 cells has no significant inhibitory effect in the induction of cell proliferation or cell cycle progression, indicating that FosB/SF is not a negative regulator of cell growth. This conclusion is further confirmed by the observation that the majority of the Jun molecules are complexed with FosB/SF in the FosB/SF-overexpressing cells.

scholarly journals Heat Shock Protein Hsp72 Is a Negative Regulator of Apoptosis Signal-Regulating Kinase 1

2002 ◽  
Vol 22 (22) ◽  
pp. 7721-7730 ◽  
Author(s):  
Hee-Sae Park ◽  
Ssang-Goo Cho ◽  
Chang Kyun Kim ◽  
Hyun Sub Hwang ◽  
Kyung Tae Noh ◽  
...  
Keyword(s):  
Heat Shock ◽  
Protein Kinase ◽  
Heat Shock Protein ◽  
Mapk Signaling ◽  
Negative Regulator ◽  
Physical Interaction ◽  
3T3 Cells ◽  
Mild Heat ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ABSTRACT Heat shock protein 72 (Hsp72) is thought to protect cells against cellular stress. The protective role of Hsp72 was investigated by determining the effect of this protein on the stress-activated protein kinase signaling pathways. Prior exposure of NIH 3T3 cells to mild heat shock (43°C for 20 min) resulted in inhibition of H2O2-induced activation of apoptosis signal-regulating kinase 1 (ASK1). Overexpression of Hsp72 also inhibited H2O2-induced activation of ASK1 as well as that of downstream kinases in the p38 mitogen-activated protein kinase (MAPK) signaling cascade. Recombinant Hsp72 bound directly to ASK1 and inhibited ASK1 activity in vitro. Furthermore, coimmunoprecipitation analysis revealed a physical interaction between endogenous Hsp72 and ASK1 in NIH 3T3 cells exposed to mild heat shock. Hsp72 blocked both the homo-oligomerization of ASK1 and ASK1-dependent apoptosis. Hsp72 antisense oligonucleotides prevented the inhibitory effects of mild heat shock on H2O2-induced ASK1 activation and apoptosis. These observations suggest that Hsp72 functions as an endogenous inhibitor of ASK1.

Metabolism of n-6 fatty acids by NIH-3T3 cells transfected with the ras oncogene

1994 ◽  
Vol 139 (1) ◽  
pp. 71-81 ◽  
Author(s):  
R. J. de Antueno ◽  
R. C. Cantrill ◽  
Y-S. Huang ◽  
G. W. Ells ◽  
M. Elliot ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Ras Oncogene ◽  
3T3 Cells ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

scholarly journals Retinoic Acid Down-regulation of Fibronectin and Retinoic Acid Receptor Proteins in NIH-3T3 Cells

1996 ◽  
Vol 271 (11) ◽  
pp. 6502-6508 ◽  
Author(s):  
Giorgio Scita ◽  
Nadine Darwiche ◽  
Eileen Greenwald ◽  
Miriam Rosenberg ◽  
Katerina Politi ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
3T3 Cells ◽  
Down Regulation ◽  
Acid Receptor ◽  
Receptor Proteins ◽  
Nih 3T3 ◽  
Nih 3T3 Cells
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