Protein Information

Name MEK1
Synonyms Dual specificity mitogen activated protein kinase kinase 1; ERK activator kinase 1; MAP kinase kinase 1; MAP2K1; MAPK/ERK kinase 1; MAPKK 1; MAPKK1; MEK 1…

Compound Information

Name cycloheximide
CAS

Reference List

PubMed Abstract RScore(About this table)
16495213 Carraro-Lacroix LR, Ramirez MA, Zorn TM, Reboucas NA, Malnic G: Increased NHE1 expression is associated with serum deprivation-induced differentiation in immortalized rat proximal tubule cells. Am J Physiol Renal Physiol. 2006 Jul;291(1):F129-39. Epub 2006 Feb 21.


The altered activity of NHE1 was consistent with an increase of both transcription and translation of the antiporter, as the utilization of actinomycin D and cycloheximide significantly inhibited the upregulation of NHE1 induced by serum withdrawal.
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18336852 Lin CC, Tseng HW, Hsieh HL, Lee CW, Wu CY, Cheng CY, Yang CM: Tumor necrosis factor-alpha induces MMP-9 expression via p42/p44 MAPK, JNK, and nuclear factor-kappaB in A549 cells. Toxicol Appl Pharmacol. 2008 Jun 15;229(3):386-98. Epub 2008 Feb 9.


Moreover, pretreatment with actinomycin D and cycloheximide attenuated TNF-alpha-induced MMP-9 expression.
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17197193 Fritzenwanger M, Meusel K, Foerster M, Kuethe F, Krack A, Figulla HR: Cardiotrophin-1 induces interleukin-6 synthesis in human umbilical vein endothelial cells. Cytokine. 2006 Nov;36(3-4):101-6. Epub 2007 Jan 2.

For the pathway determination following inhibitors were used: piceatannol (signal transducer and activation of transcription (STAT) 3 phosphorylation), wortmannin (phosphatiylinositol 3-kinase (PI3K)), SB203580 (p38 mitogen-activated protein kinase (MAPK)), AG490 (Janus kinase (JAK) 2), PD98059 (mitogen-activated protein kinase kinase (MEK) 1/2), parthenolide (nuclear factor kappaB) and cycloheximide (protein biosynthesis).
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18474417 Zanotto-Filho A, Cammarota M, Gelain DP, Oliveira RB, Delgado-Canedo A, Dalmolin RJ, Pasquali MA, Moreira JC: Retinoic acid induces apoptosis by a non-classical mechanism of ERK1/2 activation. Toxicol In Vitro. 2008 Aug;22(5):1205-12. Epub 2008 Apr 7.

ERK1/2 activation was mediated by MEK1/2, and the protein synthesis inhibitor cycloheximide did not alter the pattern of RA-induced ERK1/2 phosphorylation.
Pharmacological inhibition of MEK1/2-ERK1/2 pathway with UO126 blocked caspase-3 activation, decreased AP-1 binding to DNA and inhibited apoptosis.
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15714461 Shi YH, Wang YX, Bingle L, Gong LH, Heng WJ, Li Y, Fang WG: In vitro study of HIF-1 activation and VEGF release by bFGF in the T47D breast cancer cell line under normoxic conditions: involvement of PI-3K/Akt and MEK1/ERK pathways. J Pathol. 2005 Mar;205(4):530-6.

In addition, the translation inhibitor cycloheximide confirmed that bFGF-induced HIF-1alpha protein expression was due to de novo protein synthesis.
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15728510 Molnarfi N, Hyka-Nouspikel N, Gruaz L, Dayer JM, Burger D: The production of IL-1 receptor antagonist in IFN-beta-stimulated human monocytes depends on the activation of phosphatidylinositol 3-kinase but not of STAT1. J Immunol. 2005 Mar 1;174(5):2974-80.

In this study, the role of PI3K, MEK1, and STAT1 in IFN-beta-induced sIL-1Ra production is investigated in freshly isolated human blood monocytes.
The use of cycloheximide and actinomycin D shows that sIL-1Ra was an immediate early gene induced by IFN-beta and that PI3K was controlling sIL-1Ra gene transcription.
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18417718 Lee MJ, Lin H, Liu CW, Wu MH, Liao WJ, Chang HH, Ku HC, Chien YS, Ding WH, Kao YH: Octylphenol stimulates resistin gene expression in 3T3-L1 adipocytes via the estrogen receptor and extracellular signal-regulated kinase pathways. Am J Physiol Cell Physiol. 2008 Jun;294(6):C1542-51. Epub 2008 Apr 16.

While octylphenol was shown to increase activities of the estrogen receptor (ER) and MEK1, signaling was demonstrated to be blocked by pretreatment with either ICI-182780 (an ERalpha antagonist) or U-0126 (a MEK1 inhibitor), in which both inhibitors prevented octylphenol-stimulated phosphorylation of ERK.
The basal half-life of resistin protein induced by cycloheximide was lengthened by octylphenol treatment, suggesting that octylphenol decreases the rate of resistin protein degradation.
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16159906 Liu HS, Chen YH, Hung PF, Kao YH: Inhibitory effect of green tea (-)-epigallocatechin gallate on resistin gene expression in 3T3-L1 adipocytes depends on the ERK pathway. Am J Physiol Endocrinol Metab. 2006 Feb;290(2):E273-81. Epub 2005 Sep 13.

Overexpression with MEK1 blocked EGCG-inhibited Rstn mRNA expression.
Treatment with cycloheximide did not prevent EGCG-suppressed Rstn mRNA levels, which suggests that the effect of EGCG does not require new protein synthesis.
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19770273 Steinmann J, Halldorsson S, Agerberth B, Gudmundsson GH: Phenylbutyrate induces antimicrobial peptide expression. Antimicrob Agents Chemother. 2009 Dec;53(12):5127-33. Epub 2009 Sep 21.


Furthermore, we have demonstrated that inhibition of the mitogen-activated protein kinases MEK1/2 and c-Jun N-terminal kinase attenuate PBA-induced CAMP gene expression.
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19286921 Croons V, Martinet W, Herman AG, Timmermans JP, De Meyer GR: The protein synthesis inhibitor anisomycin induces macrophage apoptosis in rabbit atherosclerotic plaques through p38 mitogen-activated protein kinase. J Pharmacol Exp Ther. 2009 Jun;329(3):856-64. Epub 2009 Mar 13.

The latter effect was abolished by the mitogen-activated protein kinase kinase 1/2 inhibitor U0126 [1,4-diamino-2,3-dicyano-1,4-bis (2-aminophynyltio) butadiene ethanolate], although the prevention of anisomycin-induced macrophage death by SB202190 remained unchanged.
We showed recently that the protein synthesis inhibitor cycloheximide, in contrast to puromycin, selectively depleted macrophages in rabbit atherosclerotic plaques without affecting smooth muscle cells (SMCs).
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18347988 Doubravska L, Simova S, Cermak L, Valenta T, Korinek V, Andera L: Wnt-expressing rat embryonic fibroblasts suppress Apo2L/TRAIL-induced apoptosis of human leukemia cells. Apoptosis. 2008 Apr;13(4):573-87. Epub 2008 Mar 18.


This anti-apoptotic signaling was significantly hampered by the inhibition of the MEK1/ERK1/2 or NFkappaB pathways in KM3 and REH cells.
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15585589 Chen YH, Hung PF, Kao YH: IGF-I downregulates resistin gene expression and protein secretion. . Am J Physiol Endocrinol Metab. 2005 May;288(5):E1019-27. Epub 2004 Dec 7.

These data demonstrate that IGF-I downregulates Rstn gene expression via IGF-IR-dependent and MEK1-, p38 MAPK-, and phosphoinositide 3-kinase-independent pathways and likely modifies the distribution of Rstn protein between the intracellular and extracellular compartments via a p38 MAPK-dependent pathway.
Treatment with cycloheximide, but not with actinomycin D, prevented IGF-I-suppressed Rstn mRNA expression, suggesting that IGF-I destabilizes Rstn mRNA and that IGF-I's effect requires new protein, but not mRNA, synthesis.
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17097066 Lee TJ, Lee JT, Park JW, Kwon TK: Acquired TRAIL resistance in human breast cancer cells are caused by the sustained cFLIP (L) and XIAP protein levels and ERK activation. Biochem Biophys Res Commun. 2006 Dec 29;351(4):1024-30. Epub 2006 Nov 7.

The selected TRAIL-resistant cells were cross-resistant to TNF-alpha/cycloheximide but remained sensitive to DNA-damage drugs such as oxaliplatin and etoposide.
Pretreatment with PD98059 or transfection of MKK1-DN (dominant negative) expression vector attenuated TRAIL resistance in MDA-231/TR cells.
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19307750 Nakamura M, Ozaki T, Ishii A, Konishi M, Tsubota Y, Furui T, Tsuda H, Mori I, Ota K, Kakudo K: Calcitonin induces connective tissue growth factor through ERK1/2 signaling in renal tubular cells. Exp Mol Med. 2009 May 31;41(5):307-15.

Furthermore, we found that CT-mediated induction of the gene was not inhibited by cycloheximide, which suggests that CTGF gene was not induced by an increased synthesis of regulating proteins.
We further demonstrated that the regulation of CTGF gene expression by CT involved the ERK1/2 pathway, because PD98059, a MEK1 inhibitor, partially inhibited the mRNA expression of CTGF induced by CT.
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16753025 Li CF, Hughes-Fulford M: Fibroblast growth factor-2 is an immediate-early gene induced by mechanical stress in osteogenic cells. J Bone Miner Res. 2006 Jun;21(6):946-55.

Pretreatment of MC3T3-E1 cells with cycloheximide showed that the induction of fgf-2 did not require new protein synthesis.
Pretreating MC3T3-E1 cells with the mitogen-activated protein kinase (MAPK)/ERK kinase 1/2 (MEK1/2) inhibitor, U0126, or H-89, a PKA inhibitor, significantly inhibited the induction of fgf-2, showing that mechanical induction of fgf-2 is dependent on ERK and PKA signaling pathways.
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16378625 Wu CC, Hsu MC, Hsieh CW, Lin JB, Lai PH, Wung BS: Upregulation of heme oxygenase-1 by Epigallocatechin-3-gallate via the phosphatidylinositol 3-kinase/Akt and ERK pathways. Life Sci. 2006 May 15;78(25):2889-97. Epub 2005 Dec 27.

In addition, pharmacological inhibitors of phosphatidylinositol 3-kinase and MEK1/2, which are upstream of Akt and ERK1/2, respectively, attenuate EGCG-induced HO-1 expression.
Furthermore, EGCG-mediated HO-1 induction was abrogated in the presence of actinomycin D and cycloheximide, indicating that this upregulation of HO-1 occurred at the transcriptional level.
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16198345 Lim WC, Park M, Bahn JJ, Inoue H, Lee YJ: Hypertonic sodium chloride induction of cyclooxygenase-2 occurs independently of NF-kappaB and is inhibited by the glucocorticoid receptor in A549 cells. FEBS Lett. 2005 Oct 10;579(24):5430-6.

This induction was a transcriptional event that occurred in the absence of the protein synthesis inhibitor cycloheximide and was the result of enhanced promoter activity, as examined with the use of full-length COX-2 promoter-driven reporter plasmids.
The p38 MAPK inhibitor, SB203580, or MEK1/2 inhibitor, U0126, inhibited hypertonic induction of COX-2 expression.
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16043662 Rude MK, Duhaney TA, Kuster GM, Judge S, Heo J, Colucci WS, Siwik DA, Sam F: Aldosterone stimulates matrix metalloproteinases and reactive oxygen species in adult rat ventricular cardiomyocytes. Hypertension. 2005 Sep;46(3):555-61. Epub 2005 Jul 25.


U0126 (10 micromol/L), an MEK1/2 inhibitor, abolished the aldosterone-induced increase in MMP activities.
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17208589 Ito I, Laporte JD, Fiset PO, Asai K, Yamauchi Y, Martin JG, Hamid Q: Downregulation of a disintegrin and metalloproteinase 33 by IFN-gamma in human airway smooth muscle cells. J Allergy Clin Immunol. 2007 Jan;119(1):89-97. Epub 2006 Oct 23.

The reduction by IFN-gamma was partially restored by U0126, inhibitor for mitogen-activated protein kinase kinase 1/2, suggesting a role for extracellular signal-regulated kinase pathway.
Further studies using cycloheximide and actinomycin-D suggested that the downregulation was at the transcriptional level.
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19411256 Liu R, Zheng HQ, Zhou Z, Dong JT, Chen C: KLF5 promotes breast cell survival partially through fibroblast growth factor-binding protein 1-pERK-mediated dual specificity MKP-1 protein phosphorylation and stabilization. J Biol Chem. 2009 Jun 19;284(25):16791-8. Epub 2009 May 1.

By cycloheximide chase assays, we found that KLF5 decreases MKP-1 protein degradation via activating the ERK signaling.
Additionally, constitutive activation of ERK by constitutively activated MEK1 rescues the KLF5 depletion-induced MKP-1 down-regulation.
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20351270 Rosenberger S, Arce JD, Langbein L, Steenbergen RD, Rosl F: Alternative splicing of human papillomavirus type-16 E6/E6* early mRNA is coupled to EGF signaling via Erk1/2 activation. Proc Natl Acad Sci U S A. 2010 Mar 29.

Time-course experiments and incubation with cycloheximide demonstrated that E6 alternative splicing is a direct and reversible effect of EGF signal transduction, not depending on de novo protein synthesis.
Within this process, Erk1/2-kinase activation was the critical event for E6 exon inclusion, mediated by the upstream MAP kinase MEK1/2.
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15736126 Tan X, Wang YC, Sun QY, Peng A, Chen DY, Tang YZ: Effects of MAP kinase pathway and other factors on meiosis of Urechis unicinctus eggs. Mol Reprod Dev. 2005 May;71(1):67-76.


Phosphorylation of the protein was not depressed by protein synthesis inhibitor Cycloheximide (CHX), but was depressed by the MEK1 inhibitor PD98059.
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18196969 Pyo JO, Nah J, Kim HJ, Lee HJ, Heo J, Lee H, Jung YK: Compensatory activation of ERK1/2 in Atg5-deficient mouse embryo fibroblasts suppresses oxidative stress-induced cell death. Autophagy. 2008 Apr 1;4(3):315-21. Epub 2008 Jan 7.


On the contrary, Atg5-/- MEFs were as sensitive to tumor necrosis factor (TNF)-alpha and cycloheximide as WT cells, and were more sensitive to cell death triggered by amino acid-deprivation than WT MEFs.
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16109713 Rahmani M, Davis EM, Bauer C, Dent P, Grant S: Apoptosis induced by the kinase inhibitor BAY 43-9006 in human leukemia cells involves down-regulation of Mcl-1 through inhibition of translation. J Biol Chem. 2005 Oct 21;280(42):35217-27. Epub 2005 Aug 18.


Inhibition of protein synthesis by cycloheximide or proteasome function with MG132 and pulse-chase studies with [35S] methionine demonstrated that BAY 43-9006 did not diminish Mcl-1 protein stability, nor did it enhance Mcl-1 ubiquitination, but instead markedly attenuated Mcl-1 translation in association with the rapid and potent dephosphorylation of the eIF4E translation initiation factor.
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18422969 Necela BM, Su W, Thompson EA: Toll-like receptor 4 mediates cross-talk between peroxisome proliferator-activated receptor gamma and nuclear factor-kappaB in macrophages. Immunology. 2008 Nov;125(3):344-58. Epub 2008 Apr 18.


Inhibition of PPARgamma expression was not blocked by cycloheximide, indicating that de novo protein synthesis is not required for LPS-mediated suppression of PPARgamma.
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18708082 Luo SF, Lin CC, Chen HC, Lin WN, Lee IT, Lee CW, Hsiao LD, Yang CM: Involvement of MAPKs, NF-kappaB and p300 co-activator in IL-1beta-induced cytosolic phospholipase A2 expression in canine tracheal smooth muscle cells. Toxicol Appl Pharmacol. 2008 Nov 1;232(3):396-407. Epub 2008 Jul 29.


IL-1beta-induced cPLA2 expression and PGE2 production was inhibited by actinomycin D and cycloheximide, indicating the involvement of transcriptional and translational events in these responses.
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