Protein Information

Name mammalian target of rapamycin
Synonyms FK506 binding protein 12 rapamycin complex associated protein 1; FK506 binding protein 12 rapamycin associated protein 1; FKBP12 rapamycin complex associated protein 1; FKBP12 rapamycin complex associated protein; FRAP; FRAP 1; FRAP 2; FRAP1…

Compound Information

Name cycloheximide
CAS

Reference List

PubMed Abstract RScore(About this table)
16109729 Vickers CA, Dickson KS, Wyllie DJ: Induction and maintenance of late-phase long-term potentiation in isolated dendrites of rat hippocampal CA1 pyramidal neurones. J Physiol. 2005 Nov 1;568(Pt 3):803-13. Epub 2005 Aug 18.

Incubation of the slices with the mRNA translation inhibitor cycloheximide or the mammalian target of rapamycin (mTOR) inhibitor rapamycin blocked late-LTP in both 'intact' and 'isolated' slice preparations.
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18479958 Lee MY, Han HJ: Galectin-1 upregulates glucose transporter-1 expression level via protein kinase C, phosphoinositol-3 kinase, and mammalian target of rapamycin pathways in mouse embryonic stem cells. Int J Biochem Cell Biol. 2008;40(11):2421-30. Epub 2008 Apr 6.

Moreover, galectin-1 increased glucose transporter-1 mRNA and protein expression levels, which were inhibited by a disruption in transcription by actinomycin D and translation by the cycloheximide.
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20038583 Guntur KV, Guilherme A, Xue L, Chawla A, Czech MP: Map4k4 negatively regulates peroxisome proliferator-activated receptor (PPAR) gamma protein translation by suppressing the mammalian target of rapamycin (mTOR) signaling pathway in cultured adipocytes. J Biol Chem. 2010 Feb 26;285(9):6595-603. Epub 2009 Dec 28.

PPARgamma degradation rates are remarkably rapid as measured in the presence of cycloheximide (t (1/2) = 2 h), but silencing Map4k4 had no effect on PPARgamma degradation.
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18565131 Arayatrakoollikit U, Pavasant P, Yongchaitrakul T: Thrombin induces osteoprotegerin synthesis via phosphatidylinositol 3'-kinase/mammalian target of rapamycin pathway in human periodontal ligament cells. J Periodontal Res. 2008 Oct;43(5):537-43. Epub 2008 Jun 28.

The inductive effect was inhibited by cycloheximide, but not by indomethacin.
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15805247 Cinar B, De Benedetti A, Freeman MR: Post-transcriptional regulation of the androgen receptor by Mammalian target of rapamycin. Cancer Res. 2005 Apr 1;65(7):2547-53.

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17032741 Finlay D, Ruiz-Alcaraz AJ, Lipina C, Perrier S, Sutherland C: A temporal switch in the insulin-signalling pathway that regulates hepatic IGF-binding protein-1 gene expression. J Mol Endocrinol. 2006 Oct;37(2):227-37.


We havepreviously shownthat the insulin regulationof hepatic IGF-binding protein-1 (IGFBP1) expression requiresthe signalling proteins phosphatidylinositol 3-kinase (PI 3-kinase) and mammalian target of rapamycin (mTOR).
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16506055 Doronzo G, Russo I, Mattiello L, Riganti C, Anfossi G, Trovati M: Insulin activates hypoxia-inducible factor-1alpha in human and rat vascular smooth muscle cells via phosphatidylinositol-3 kinase and mitogen-activated protein kinase pathways: impairment in insulin resistance owing to defects in insulin signalling. Diabetologia. 2006 May;49(5):1049-63. Epub 2006 Feb 28.

METHODS: Using aortic VSMC taken from humans and Zucker rats and cultured in normoxia, the following were evaluated: (1) dose-dependent (0.5, 1, 2 nmol/l) and time-dependent (2, 4, 6 h) effects exerted by insulin on HIF-1alpha content in both nucleus and cytosol, measured by Western blots; (2) insulin effects on HIF-1 DNA-binding activity on the VEGF gene, measured by electrophoretic mobility shift assay; and (3) involvement of the insulin signalling molecules in these insulin actions, by using the following inhibitors: LY294002 (PI3-K), PD98059 (extracellular signal regulated kinase [ERK]), SP600125 (Jun N terminal kinase [JNK]), SB203580 (p38 mitogen-activated protein kinase) and rapamycin (mammalian target of rapamycin), and by detecting the insulin signalling molecules by Western blots.
The insulin-induced increase of HIF-1alpha is blunted by the translation inhibitor cycloheximide, LY294002, PD98059, SP600125 and rapamycin, but not by SB203580.
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15772076 Smith EM, Finn SG, Tee AR, Browne GJ, Proud CG: The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses. J Biol Chem. 2005 May 13;280(19):18717-27. Epub 2005 Mar 16.


Amino acids positively regulate signaling through the mammalian target of rapamycin (mTOR).
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19074679 Huang BP, Wang Y, Wang X, Wang Z, Proud CG: Blocking eukaryotic initiation factor 4F complex formation does not inhibit the mTORC1-dependent activation of protein synthesis in cardiomyocytes. Am J Physiol Heart Circ Physiol. 2009 Feb;296(2):H505-14. Epub 2008 Dec 12.


Activation of the mammalian target of rapamycin complex 1 (mTORC1) causes the dissociation of eukaryotic initiation factor 4E complex (eIF4E)-binding protein 1 (4E-BP1) from eIF4E, leading to increased eIF4F complex formation. mTORC1 positively regulates protein synthesis and is implicated in several diseases including cardiac hypertrophy, a potentially fatal disorder involving increased cardiomyocyte size.
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17606477 MacManus CF, Pettigrew J, Seaton A, Wilson C, Maxwell PJ, Berlingeri S, Purcell C, McGurk M, Johnston PG, Waugh DJ: Interleukin-8 signaling promotes translational regulation of cyclin D in androgen-independent prostate cancer cells. Mol Cancer Res. 2007 Jul;5(7):737-48. Epub 2007 Jul 2.

Administration of recombinant human IL-8 induced a rapid, time-dependent increase in cyclin D1 expression in AIPC cells, a response attenuated by the translation inhibitor cycloheximide but not by the RNA synthesis inhibitor, actinomycin D.
Immunoblotting using phospho-specific antibodies confirmed that recombinant human IL-8 induced rapid time-dependent phosphorylation of Akt and the mammalian target of rapamycin substrate proteins, 4E-BP1 and ribosomal S6 kinase, resulting in a downstream phosphorylation of the ribosomal S6 protein (rS6).
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16464865 Chong-Kopera H, Inoki K, Li Y, Zhu T, Garcia-Gonzalo FR, Rosa JL, Guan KL: TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the HERC1 ubiquitin ligase. J Biol Chem. 2006 Mar 31;281(13):8313-6. Epub 2006 Feb 7.


The TSC1 and TSC2 proteins, also called hamartin and tuberin, respectively, have been shown to regulate cell growth through inhibition of the mammalian target of rapamycin pathway.
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18024516 Braun PR, Al-Younes H, Gussmann J, Klein J, Schneider E, Meyer TF: Competitive inhibition of amino acid uptake suppresses chlamydial growth: involvement of the chlamydial amino acid transporter BrnQ. J Bacteriol. 2008 Mar;190(5):1822-30. Epub 2007 Nov 16.


Our experiments revealed that the antichlamydial effects are largely independent of changes in the host cell transcriptome or proteome and in the major signal transduction pathway modulated by amino acids, the mTOR (mammalian target of rapamycin) pathway.
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16507764 Hui AS, Bauer AL, Striet JB, Schnell PO, Czyzyk-Krzeska MF: Calcium signaling stimulates translation of HIF-alpha during hypoxia. . FASEB J. 2006 Mar;20(3):466-75.


This requires influx of extracellular calcium, stimulation of classical protein kinase C-alpha (cPKC-alpha), and the activity of mammalian target of rapamycin, mTOR.
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18223253 Carayol N, Katsoulidis E, Sassano A, Altman JK, Druker BJ, Platanias LC: Suppression of programmed cell death 4 (PDCD4) protein expression by BCR-ABL-regulated engagement of the mTOR/p70 S6 kinase pathway. J Biol Chem. 2008 Mar 28;283(13):8601-10. Epub 2008 Jan 26.


There is accumulating evidence that mammalian target of rapamycin (mTOR)-activated pathways play important roles in cell growth and survival of BCR-ABL-transformed cells.
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18070882 Kimball SR, Do AN, Kutzler L, Cavener DR, Jefferson LS: Rapid turnover of the mTOR complex 1 (mTORC1) repressor REDD1 and activation of mTORC1 signaling following inhibition of protein synthesis. J Biol Chem. 2008 Feb 8;283(6):3465-75. Epub 2007 Dec 10.

mTORC1 is a complex of proteins that includes the mammalian target of rapamycin (mTOR) and several regulatory proteins.
Moreover the cycloheximide-induced increase in mTORC1 signaling was significantly attenuated in cells lacking REDD1, showing that REDD1 plays an integral role in the response.
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19787057 Sung MH, Salvatore L, De Lorenzi R, Indrawan A, Pasparakis M, Hager GL, Bianchi ME, Agresti A: Sustained oscillations of NF-kappaB produce distinct genome scanning and gene expression profiles. PLoS One. 2009 Sep 29;4(9):e7163.


The ability of NF-kappaB to scan and interact with the genome in vivo remained remarkably constant from early to late cycles, as observed by fluorescence recovery after photobleaching (FRAP).
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17683115 Fernandez N, Gonzalez A, Valera I, Alonso S, Crespo MS: Mannan and peptidoglycan induce COX-2 protein in human PMN via the mammalian target of rapamycin. Eur J Immunol. 2007 Sep;37(9):2572-82.

Treatment with the phosphatidylinositol 3-kinase inhibitor (PI3K) wortmaninn, the mammalian target of rapamycin (mTOR) inhibitor rapamycin, and the translation inhibitor cycloheximide blocked the induction of COX-2 protein in response to mannan and PGN, whereas the transcriptional inhibitor actinomycin D did not show a significant effect.
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16310186 van Zon A, Mossink MH, Houtsmuller AB, Schoester M, Scheffer GL, Scheper RJ, Sonneveld P, Wiemer EA: Vault mobility depends in part on microtubules and vaults can be recruited to the nuclear envelope. Exp Cell Res. 2006 Feb 1;312(3):245-55. Epub 2005 Nov 28.

Using quantitative fluorescence-recovery after photobleaching (FRAP), we demonstrated that vault mobility over longer distances in part depends on intact microtubules; vaults moving slower when microtubules are depolymerized by nocodazole.
We observed an accumulation of vaults at the nuclear envelope upon treatment of cells with the protein synthesis inhibitor cycloheximide.
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17135342 Croons V, Martinet W, Herman AG, Timmermans JP, De Meyer GR: Selective clearance of macrophages in atherosclerotic plaques by the protein synthesis inhibitor cycloheximide. J Pharmacol Exp Ther. 2007 Mar;320(3):986-93. Epub 2006 Nov 29.

We have demonstrated previously that local delivery of the mammalian target of rapamycin (mTOR) inhibitor everolimus selectively clears macrophages in rabbit plaques.
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16859513 Shapira M, Kakiashvili E, Rosenberg T, Hershko DD: The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells. Breast Cancer Res. 2006;8(4):R46.

The mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphoinositol 3' kinase (PI3K)/Akt pathway that down-regulates p27 levels in breast cancer.
The effect of rapamycin on the degradation rate of Skp2 expression was examined in cycloheximide-treated cells and in relationship to the anaphase promoting complex/Cdh1 (APC\C) inhibitor Emi1.
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18160716 Wang X, Proud CG: A novel mechanism for the control of translation initiation by amino acids, mediated by phosphorylation of eukaryotic initiation factor 2B. Mol Cell Biol. 2008 Mar;28(5):1429-42. Epub 2007 Dec 26.


Although amino acid deprivation also inhibits signaling through the mammalian target of rapamycin complex 1 (mTORC1), the inhibition of eIF2B activity by amino acid starvation is independent of mTORC1.
1(0,0,0,1) Details
19557001 Katiyar S, Liu E, Knutzen CA, Lang ES, Lombardo CR, Sankar S, Toth JI, Petroski MD, Ronai Z, Chiang GG: REDD1, an inhibitor of mTOR signalling, is regulated by the CUL4A-DDB1 ubiquitin ligase. EMBO Rep. 2009 Aug;10(8):866-72. Epub 2009 Jun 26.


REDD1 (regulated in development and DNA damage responses 1), a hypoxia-inducible factor-1 target gene, has a crucial role in inhibiting mammalian target of rapamycin complex 1 (mTORC1) signalling during hypoxic stress.
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18466319 Santa-Catalina MO, Garcia-Marin LJ, Bragado MJ: Lovastatin effect in rat neuroblasts of the CNS: inhibition of cap-dependent translation. J Neurochem. 2008 Aug;106(3):1078-91. Epub 2008 May 3.

Cycloheximide treatment, which blocked protein synthesis, does not induce neuroblasts apoptosis.
Lovastatin treatment in rat brain neuroblasts causes a significant time- and concentration-inhibition of protein synthesis, which is partially mediated by phosphatydilinositol 3-kinase/mammalian target of rapamycin (mTOR) pathway inhibition.
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18199701 King MA, Hands S, Hafiz F, Mizushima N, Tolkovsky AM, Wyttenbach A: Rapamycin inhibits polyglutamine aggregation independently of autophagy by reducing protein synthesis. Mol Pharmacol. 2008 Apr;73(4):1052-63. Epub 2008 Jan 16.


It is noteworthy that the mammalian target of rapamycin inhibitor rapamycin or its analogs have been proposed as promising therapeutic compounds clearing toxic protein assemblies in these diseases via activation of autophagy.
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16431369 Forster R, Weiss M, Zimmermann T, Reynaud EG, Verissimo F, Stephens DJ, Pepperkok R: Secretory cargo regulates the turnover of COPII subunits at single ER exit sites. Curr Biol. 2006 Jan 24;16(2):173-9.


A mathematical model of COPII membrane turnover that reproduces the experimental in vivo FRAP kinetics and is consistent with existing in vitro data predicts that Sec23/24p remains membrane associated even after GTP hydrolysis by Sar1p for a duration that is strongly increased by the presence of cargo.
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17259394 Mariappan MM, Feliers D, Mummidi S, Choudhury GG, Kasinath BS: High glucose, high insulin, and their combination rapidly induce laminin-beta1 synthesis by regulation of mRNA translation in renal epithelial cells. Diabetes. 2007 Feb;56(2):476-85.

Cycloheximide, but not actinomycin-D, abrogated increased laminin-beta1 synthesis.
High glucose, high insulin, and high glucose+high insulin stimulated phosphorylation of 4E-BP1, a repressor binding protein for eukaryotic initiation factor 4E (eIF4E), that was dependent on activation of phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin.
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18493739 Wang Q, Heimberg H, Pipeleers D, Ling Z: Glibenclamide activates translation in rat pancreatic beta cells through calcium-dependent mTOR, PKA and MEK signalling pathways. Diabetologia. 2008 Jul;51(7):1202-12. Epub 2008 May 21.

Since it was blocked by the translation inhibitor cycloheximide, we examined whether sustained exposure to glibenclamide activates translational factors by calcium-dependent signalling pathways.
This activation of translational factors and the associated elevation of insulin synthesis were completely blocked by the calcium channel blocker verapamil and partially blocked by the mammalian target of rapamycin (mTOR) inhibitor rapamycin, the protein kinase A (PKA) inhibitor Rp-8-Br-cAMPs and the mitogen-activated protein kinase/ extracellular signal-regulated kinase kinase (MEK) inhibitor U0126; a combination of inhibitors exhibited additive effects.
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17804721 Endo H, Murata K, Mukai M, Ishikawa O, Inoue M: Activation of insulin-like growth factor signaling induces apoptotic cell death under prolonged hypoxia by enhancing endoplasmic reticulum stress response. Cancer Res. 2007 Sep 1;67(17):8095-103.

Mammalian target of rapamycin (mTOR), one of the downstream molecules of the insulin-like growth factor (IGF) pathway, is a key regulator of translation, integrating multiple environmental and nutritional cues.
IGF-induced cell death under hypoxic conditions was prevented by treatment with cycloheximide, suggesting that de novo protein synthesis is required.
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19718660 Ranzato E, Grosso S, Patrone M, Betta PG, Viarengo A, Biffo S: Spreading of mesothelioma cells is rapamycin-sensitive and requires continuing translation. J Cell Biochem. 2009 Nov 1;108(4):867-76.

Spreading of cancer cells on fibronectin does not require de novo transcription but is sensitive to cycloheximide, an inhibitor of protein synthesis.
Next, we analyzed the involvement of the mammalian target of rapamycin (mTOR) pathway, a major pathway controlling translation.
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20036288 Nadezhdina ES, Lomakin AJ, Shpilman AA, Chudinova EM, Ivanov PA: Microtubules govern stress granule mobility and dynamics. Biochim Biophys Acta. 2010 Mar;1803(3):361-371. Epub 2009 Dec 28.


In cycloheximide-treated cells SGs dissociated into constituent parts that then dissolved within the cytoplasm.
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