Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:Q9UID6 (
Kruppel-like
)
147
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Phorbol 12-myristate 13-acetate (PMA) modulates cell proliferation and survival by activating several intracellular signaling pathways. Protein kinase C (PKC) plays a key role in PMA-induced growth arrest of non-small cell lung cancer (NSCLC) cells.
Kruppel-like
transcription factor 6 (KLF6), which is associated with negative control of cell proliferation, is downregulated in many cancers, including NSCLC. In this study, we found that KLF6 is downregulated in 17 lung cancer cell lines and in cells representing early stages of lung cancer development. Moreover, PMA induced cell growth arrest through KLF6 induction in H358 NSCLC cells. The increase in KLF6 by PMA was associated with upregulation of the cyclin-dependent kinase inhibitors (CDKIs) p21(WAF1/CIP1) and p27(KIP1). In addition, inhibition of PKC or
JNK
activation decreased PMA-induced KLF6 induction and activation of PKC alone by Bryostatin-1 and Thymeleatoxin increased KLF6 levels. Moreover, siRNA-mediated knockdown of KLF6 reduced PMA-induced cell growth inhibition concomitantly with decreased expression of both p21(WAF1/CIP1) and p27(KIP1), and in accordance, overexpression of KLF6 alone upregulated both CDKIs protein levels. Our results demonstrate the induction of the tumor suppressor KLF6 following PKC activation and its importance for PMA-mediated cancer cell growth arrest.
...
PMID:Activation of protein kinase C by phorbol 12-myristate 13-acetate suppresses the growth of lung cancer cells through KLF6 induction. 1933 10
Cardiac hypertrophy is considered an early hallmark during the clinical course of heart failure and an important risk factor for cardiac morbidity and mortality. Although hypertrophy of individual cardiomyocytes in response to pathological stimuli has traditionally been considered as an adaptive response required to sustain cardiac output, accumulating evidence from studies in patients and animal models suggests that in most instances hypertrophy of the heart also harbors maladaptive aspects. Major strides have been made in our understanding of the pathways that convey pro-hypertrophic signals from the outside of the cell to the nucleus. In recent years it also has become increasingly evident that the heart possesses a variety of endogenous feedback mechanisms to counterbalance this growth response. These repressive mechanisms are of particular interest since they may provide valuable therapeutic options. In this review we summarize currently known endogenous repressors of pathological cardiac growth as they have been studied by gene targeting in mice. Many of the repressors that function in signal transduction appear to regulate calcineurin (e.g. PICOT, calsarcin, RCAN) and
JNK
signaling (e.g. CDC42, MKP-1) and some will be described in greater detail in this review. In addition, we will focus on factors such as
Kruppel-like
factors (KLF4, KLF15 and KLF10) and histone deacetylases (HDACs), which constitute a relevant group of nuclear proteins that repress transcription of the hypertrophic gene program in cardiomyocytes.
...
PMID:Tapping the brake on cardiac growth-endogenous repressors of hypertrophic signaling. 2158 93
Sodium trisulfide (Na
2
S
3
) releases hydrogen polysulfide (H
2
S
n
) and is useful for the investigation of the effects of H
2
S
n
on the cell functions. In the present study, we first examined the effects of Na
2
S
3
on the gene expression of IEC-6 cells, a rat intestinal epithelial cell line. Microarray analysis and reverse transcription-polymerase chain reaction analysis revealed that Na
2
S
3
increased the gene expression of early growth response 1 (EGR1) and
Kruppel-like
transcription factor 4 (KLF4). It was interesting that U0126, an inhibitor of the activation of extracellular signal-regulated kinase 1 (ERK1),
ERK2
, and ERK5, inhibited the Na
2
S
3
-induced gene expression of EGR1 and KLF4. Na
2
S
3
activated ERK1 and
ERK2
(ERK1/2) within 15 min. In addition to ERK1/2, Na
2
S
3
activated ERK5. We noticed that the electrophoretic mobility of ERK5 was decreased after Na
2
S
3
treatment. Phos-tag analysis and in vitro dephosphorylation of the cell extracts indicated that the gel-shift of ERK5 was due to its phosphorylation. The gel-shift of ERK5 was inhibited completely by both U0126 and ERK5-IN-1, a specific inhibitor of ERK5. From these results, we concluded that the gel-shift of ERK5 was induced through autophosphorylation by activated ERK5 after Na
2
S
3
treatment. The present study suggested that H
2
S
n
affected various functions of intestinal epithelial cells through the activation of the ERK1/2 and ERK5 pathways.
...
PMID:Increased expression of EGR1 and KLF4 by polysulfide via activation of the ERK1/2 and ERK5 pathways in cultured intestinal epithelial cells. 3252 29
