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: EC:3.4.11.18 (
MAP
)
7,412
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Kidney samples of male Fischer 344 (F-344) rats fed a carcinogenic dose of OTA over 7 days, 21 days and 12 months were analysed for various cell signalling proteins known to be potentially involved in chemical carcinogenicity. OTA was found to increase the phosphorylation of atypical-PKC. This was correlated with a selective downstream activation of the
MAP
-kinase extracellular regulated kinases isoforms 1 and 2 (ERK1/2) and of their substrates
ELK1
/2 and p90RSK. Moreover, analysis of effectors acting upstream of PKC indicated a possible mobilisation of the insulin-like growth factor-1 receptor (lGFr) and phosphoinositide-dependent kinase-1 (PDK1) system. An increased histone deacetylase (HDAC) enzymatic activity associated with enhanced HDAC3 protein expression was also observed. These findings are potentially relevant with respect to the understanding of OTA nephrocarcinogenicity. HDAC-induced gene silencing has previously been shown to play a role in tumour development. Furthermore, PKC and the MEK-ERK
MAP
-kinase pathways are known to play important roles in cell proliferation, cell survival, anti-apoptotic activity and renal cancer development.
...
PMID:MAPK-ERK activation in kidney of male rats chronically fed ochratoxin A at a dose causing a significant incidence of renal carcinoma. 1765 72
6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major bioactive compound in Wasabi. Although 6-MSITC is reported to have cancer chemopreventive activities in rat model, the molecular mechanism is unclear. In this study, we investigated the anticancer mechanisms using two types of human colorectal cancer cells (HCT116 p53
+/+
and p53
-/-
). 6-MSITC caused cell cycle arrest in G
2
/M phase and induced apoptosis in both types of cells in the same fashion. Signaling data revealed that the activation of ERK1/2, rather than p53, is recruited for 6-MSITC-induced apoptosis. 6-MSITC stimulated ERK1/2 phosphorylation, and then activated ERK1/2 signaling including
ELK1
phosphorylation, and upregulation of C/EBP homologous protein (CHOP) and death receptor 5 (DR5). The MEK1/2 inhibitor U0126 blocked all of these molecular events induced by 6-MSITC, and enhanced the cell viability in both types of cells in the same manner. These results indicated that ERK1/2-mediated
ELK1
/CHOP/DR5 pathway is involved in 6-MSITC-induced apoptosis in colorectal cancer cells. Abbreviations: CHOP: C/EBP homologous protein; DR5: death receptor 5;
ELK1
: ETS transcription factor; ERK1/2: extracellular signal-regulated kinase 1/2; JNK: Jun-N-terminal kinase; MAPK: mitogen-activated protein kinase; MEK1/2:
MAP
/ERK kinase 1/2; 6-MSITC: 6-(methylsulfinyl)hexyl isothiocyanate; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PARP: poly(ADP-ribose) polymerase.
...
PMID:Involvement of ERK1/2-mediated ELK1/CHOP/DR5 pathway in 6-(methylsulfinyl)hexyl isothiocyanate-induced apoptosis of colorectal cancer cells. 3073 Feb 56
