Protein Information

Name epidermal growth factor receptor
Synonyms EGF receptor; EGFR; EGFR protein; ERBB; ERBB 1; ERBB1; Epidermal growth factor receptor; Epidermal growth factor receptor isoform a variant…

Compound Information

Name cycloheximide
CAS

Reference List

PubMed Abstract RScore(About this table)
19201814 Kassel KM, Schulte NA, Toews ML: Modulation of epidermal growth factor receptor binding to human airway smooth muscle cells by glucocorticoids and beta2-adrenergic receptor agonists. Am J Physiol Lung Cell Mol Physiol. 2009 Apr;296(4):L693-9. Epub 2009 Feb 6.

Although the increase in EGFR binding was blocked by the protein synthesis inhibitor cycloheximide for LPA, fluticasone, and dexamethasone, only LPA induced a significant increase in EGFR protein expression detected by immunoblotting.
86(1,1,1,6) Details
19553664 Sommerfeld A, Reinehr R, Haussinger D: Bile acid-induced epidermal growth factor receptor activation in quiescent rat hepatic stellate cells can trigger both proliferation and apoptosis. J Biol Chem. 2009 Aug 14;284(33):22173-83. Epub 2009 Jun 24.

When, however, a JNK signal was induced by coadministration of cycloheximide or hydrogen peroxide (H2O2), activated EGFR associated with CD95 and triggered EGFR-mediated CD95-tyrosine phosphorylation and subsequent formation of the death-inducing signaling complex.
84(1,1,1,4) Details
17825525 Ray RM, Bhattacharya S, Johnson LR: EGFR plays a pivotal role in the regulation of polyamine-dependent apoptosis in intestinal epithelial cells. Cell Signal. 2007 Dec;19(12):2519-27. Epub 2007 Aug 15.

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18234969 Reznik TE, Sang Y, Ma Y, Abounader R, Rosen EM, Xia S, Laterra J: Transcription-dependent epidermal growth factor receptor activation by hepatocyte growth factor. Mol Cancer Res. 2008 Jan;6(1):139-50.

Tyr (845) and Tyr (1068) phosphorylation, in response to HGF, was inhibited by cycloheximide and actinomycin D, consistent with a requirement for DNA transcription and RNA translation.
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19168569 Andrew AS, Mason RA, Memoli V, Duell EJ: Arsenic activates EGFR pathway signaling in the lung. . Toxicol Sci. 2009 Jun;109(2):350-7. Epub 2009 Jan 23.


Phosphorylation of the epidermal growth factor receptor (EGFR) has been reported with arsenic exposure in bladder cells.
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16786197 Li Z, Zong H, Kong X, Zhang S, Wang H, Sun Q, Gu J: Cell surface beta 1, 4-galactosyltransferase 1 promotes apoptosis by inhibiting epidermal growth factor receptor pathway. Mol Cell Biochem. 2006 Oct;291(1-2):69-76. Epub 2006 Jun 20.

Our previous studies have shown that overexpression of beta1,4-galactosyltransferase1 (beta1,4GT1) leads to increased apoptosis induced by cycloheximide (CHX) in SMMC-7721 human hepatocarcinoma cells.
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15748153 Steinbach JP, Wolburg H, Klumpp A, Weller M: Hypoxia sensitizes human malignant glioma cells towards CD95L-induced cell death. J Neurochem. 2005 Mar;92(6):1340-9.

Furthermore, inhibition of protein synthesis by cycloheximide also reduced glucose consumption and conferred protection from hypoxia, but did not modulate CD95L-induced cell death under hypoxic conditions.
Inhibition of the epidermal growth factor receptor (EGFR), although sensitizing glioma cells to CD95L under normoxia, protects glioma cells from hypoxia by reducing energy consumption.
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15961274 Liu ZM, Huang HS: As2O3-induced c-Src/EGFR/ERK signaling is via Sp1 binding sites to stimulate p21WAF1/CIP1 expression in human epidermoid carcinoma A431 cells. Cell Signal. 2006 Feb;18(2):244-55. Epub 2005 Jun 14.

Finally, our experiments utilizing cycloheximide prompt the suggestion that the stability of mRNA or protein also contributes to As2O3- or EGF-induced p21 expression.
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18787018 Adams BD, Claffey KP, White BA: Argonaute-2 expression is regulated by epidermal growth factor receptor and mitogen-activated protein kinase signaling and correlates with a transformed phenotype in breast cancer cells. Endocrinology. 2009 Jan;150(1):14-23. Epub 2008 Sep 11.

Half-life studies using cycloheximide indicated that EGF enhanced, whereas U0126 decreased, Ago2 protein stability.
2(0,0,0,2) Details
19683494 Descot A, Hoffmann R, Shaposhnikov D, Reschke M, Ullrich A, Posern G: Negative regulation of the EGFR-MAPK cascade by actin-MAL-mediated Mig6/Errfi-1 induction. Mol Cell. 2009 Aug 14;35(3):291-304.


Upregulation of Mig6 by lipid agonists such as LPA and S1P or actin drugs involved MAL and correlated with decreased activation of EGFR, MAPK/Erk, and c-fos.
2(0,0,0,2) Details
17287395 Balestreire EM, Apodaca G: Apical epidermal growth factor receptor signaling: regulation of stretch-dependent exocytosis in bladder umbrella cells. Mol Biol Cell. 2007 Apr;18(4):1312-23. Epub 2007 Feb 7.

2(0,0,0,2) Details
16644694 Koehler JA, Drucker DJ: Activation of glucagon-like peptide-1 receptor signaling does not modify the growth or apoptosis of human pancreatic cancer cells. Diabetes. 2006 May;55(5):1369-79.

Conversely, Ex-4 induced extracellular regulated kinase (ERK) 1/2 activation in PL 45 cells in a GLP-1R-and epidermal growth factor receptor-dependent manner, whereas Ex-4 inhibited ERK1/2 phosphorylation in Hs 766T and CAPAN-1 cells.
Ex-4 did not modulate the proliferation of these cell lines in vitro and did not inhibit apoptosis after exposure of cells to cytotoxic agents such as cycloheximide, indomethacin, LY294002, or cyclopamine.
1(0,0,0,1) Details
19376214 Ridley W, Matsuoka M: Fluoride-induced cyclooxygenase-2 expression and prostaglandin E2 production in A549 human pulmonary epithelial cells. Toxicol Lett. 2009 Aug 10;188(3):180-5. Epub 2009 Apr 17.

NaF-induced accumulation of COX-2 transcript was abolished by actinomycin D, but not cycloheximide.
Furthermore, NaF-induced COX-2 expression was markedly suppressed by the Src family kinase (SFK) inhibitor PP2, but only partially suppressed by the epidermal growth factor receptor (EGFR) inhibitor PD153035.
1(0,0,0,1) Details
16648577 Andersson Y, Le H, Juell S, Fodstad O: AMP-activated protein kinase protects against anti-epidermal growth factor receptor-Pseudomonas exotoxin A immunotoxin-induced MA11 breast cancer cell death. Mol Cancer Ther. 2006 Apr;5(4):1050-9.

In contrast, cycloheximide, even at a concentration causing a 90% inhibition of protein synthesis, did neither affect the ATP level nor activate JNK and AMPK.
1(0,0,0,1) Details
19604397 Hugo HJ, Wafai R, Blick T, Thompson EW, Newgreen DF: Staurosporine augments EGF-mediated EMT in PMC42-LA cells through actin depolymerisation, focal contact size reduction and Snail1 induction - a model for cross-modulation. BMC Cancer. 2009 Jul 15;9:235.

Gene expression analysis by MT-PCR indicated that ST repressed many genes which were induced by EGF (EGFR, CAV1, CTGF, CYR61, CD44, S100A4) and induced genes which alter the actin cytoskeleton (NLF1, NLF2, EPHB4).
METHODS: PMC42-LA cells were treated for 72 h with 10 ng/ml EGF, 40 nM ST, or both, and assessed for expression of E-cadherin repressor genes (Snail1, Snail2, Zeb1/deltaEF1) and EMT-related genes by QRT-PCR, multiplex tandem PCR (MT-PCR) and immunofluorescence +/- cycloheximide.
1(0,0,0,1) Details
18281499 Herrmann T, Grosse-Hovest L, Otz T, Krammer PH, Rammensee HG, Jung G: Construction of optimized bispecific antibodies for selective activation of the death receptor CD95. Cancer Res. 2008 Feb 15;68(4):1221-7.

The presence of sensitizing reagents such as cycloheximide and various cytostatic drugs further enhanced antibody-mediated killing of the tumor cells.
This is most likely due to the exclusively unicellular binding of this particular fragment to target cells expressing both the epidermal growth factor receptor and CD95.
1(0,0,0,1) Details
19006119 Suh HN, Lee YJ, Han HJ: Interleukin-6 promotes 2-deoxyglucose uptake through p44/42 MAPKs activation via Ca2+/PKC and EGF receptor in primary cultured chicken hepatocytes. J Cell Physiol. 2009 Mar;218(3):643-52.

Indeed, IL-6 increased GLUT-2 mRNA and protein expression as well as 2-DG uptake, which were blocked by actinomycin D (AD, transcription inhibitor) and cycloheximide (CHX, translation inhibitor).
In addition, IL-6 increased EGFR/src/FAK, PI3K/Akt phosphorylation and 2-DG uptake as well as GLUT-2 protein expression, which were blocked by AG 1478 (EGF receptor inhibitor), PP2 (src family of tyrosine kinase inhibitor), PI3K-specific siRNA, and a Akt inhibitor.
1(0,0,0,1) Details
15619605 Gravel SP, Servant MJ: Roles of an IkappaB kinase-related pathway in human cytomegalovirus-infected vascular smooth muscle cells: a molecular link in pathogen-induced proatherosclerotic conditions. J Biol Chem. 2005 Mar 4;280(9):7477-86. Epub 2004 Dec 24.


Activation of the TBK1/IRF-3 pathway was independent of epidermal growth factor receptor and pertussis toxin-sensitive G protein-coupled receptor activation.
1(0,0,0,1) Details
17400267 Patterson TJ, Rice RH: Arsenite and insulin exhibit opposing effects on epidermal growth factor receptor and keratinocyte proliferative potential. Toxicol Appl Pharmacol. 2007 May 15;221(1):119-28. Epub 2007 Feb 14.

1(0,0,0,1) Details
19583809 Keating N, Mroz MS, Scharl MM, Marsh C, Ferguson G, Hofmann AF, Keely SJ: Physiological concentrations of bile acids down-regulate agonist induced secretion in colonic epithelial cells. J Cell Mol Med. 2009 Aug;13(8B):2293-303. Epub 2009 Jul 6.

The EGFr inhibitor, AG1478, and the protein synthesis inhibitor, cycloheximide, reversed the antisecretory effects of DCA, while the MAPK inhibitors, PD98059 and SB203580, did not.
DCA (50 microM) rapidly stimulated phosphorylation of the epidermal growth factor receptor (EGFr) and both ERK and p38 MAPKs (mitogen-activated protein kinases).
1(0,0,0,1) Details
19009649 Guller M, Toualbi-Abed K, Legrand A, Michel L, Mauviel A, Bernuau D, Daniel F: c-Fos overexpression increases the proliferation of human hepatocytes by stabilizing nuclear Cyclin D1. World J Gastroenterol. 2008 Nov 7;14(41):6339-46.

The levels of cell cycle regulatory proteins (Cyclin D1, E, A) cyclin dependent kinases (cdk) cdk2, cdk4, cdk6, and their inhibitors p15, p16, p21, p27, total and phosphorylated GSK-3beta and epidermal growth factor receptor (EGF-R) were assayed by Western blotting.
Stability of Cyclin D1 was studied by cycloheximide blockade experiments.
1(0,0,0,1) Details
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.
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