Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.25 (MEKK1)
 1,856 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Whilst many studies have examined the role of the MAP Kinases in regulating the G1-->S transition, much less is known about the function of these pathways in regulating other cell cycle transitions. Stimulation of the conditional mutant Delta MEKK3:ER* in asynchronous hamster (CCl39) and rat (Rat-1) fibroblasts resulted in the strong activation of endogenous JNK and p38 but only a weak activation of ERK. Activation of Delta MEKK3:ER* inhibited cell proliferation through a combination of an initial G1 and G2 cell cycle arrest, followed by a delayed onset of apoptosis. When cells were synchronized in S phase with aphidicolin and then released, activation of Delta MEKK3:ER* resulted in the up-regulation of p21(CIP1) and a pronounced inhibition of cyclin A/CDK2 and cyclin B1/CDK1 kinase activity. Analysis of mitotic figures indicated that cells failed to enter mitosis, arresting late in G2. Delta MEKK3:ER*-mediated CDK inhibition and G2 arrest did not absolutely require p21(CIP1), since both events were observed in Rat-1 cells in which p21(CIP1) is transcriptionally silenced due to promoter methylation. Rather, CDK inhibition was associated with a down-regulation of cyclin A and B1 expression. Finally, application of the p38 inhibitor SB203580 partially restored cyclin B associated kinase activity and allowed cells to proceed through mitosis into the next G1 phase, suggesting that activation of the p38 alpha/beta 2 pathway can promote a G2 cell cycle arrest.
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PMID:Delta MEKK3:ER* activation induces a p38 alpha/beta 2-dependent cell cycle arrest at the G2 checkpoint. 1244 45

In order to examine the effects of thioglycolic acid (TGA) on reproduction, Xenopus oocytes were treated with different concentrations of TGA. During culture, frequencies of germinal vesicle breakdown (GVBD) and MI-MII transition were determined. Samples collected at indicated times were subjected to immunoblotting. Data indicated that TGA accelerated the frequency of GVBD, but inhibited polar body extrusion and formation of MII-arrested eggs in a concentration-dependent manner. At 4 h after progesterone addition, phosphorylation of extracellular signal-regulated kinase (ERK) and p90 ribosomal S6 kinase, two members of the mitogen-activated protein kinase (MAPK) pathway, was upregulated in TGA-treated oocytes. The regulatory subunit of M-phase promoting factor (MPF)-cyclin B was also upregulated by TGA, while phospho-Cdc2 was downregulated. At 8 h, Cdc2 dephosphorylation and cyclin B1 were downregulated by TGA treatment. However, TGA exerted no effect on Mos, an MAPKKK (MAPK kinase kinase). In conclusion, TGA has the potential to inhibit in vitro maturation of Xenopus oocyte with increased GVBD frequency accompanied by alterations in protein expression and phosphorylation involved in MPF and MAPK pathways. Since egg formation is essential to maintain appropriate reproductive capacity, our findings may have certain toxicological implications.
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PMID:Effects of thioglycolic acid on progesterone-induced maturation of Xenopus oocytes. 2007 79