Protein Information

Name ubiquitin
Synonyms HMG20; RPS27A; UBA80; UBCEP 1; UBCEP1; UBA52; UBCEP 2; UBCEP2…

Compound Information

Name cycloheximide
CAS

Reference List

PubMed Abstract RScore(About this table)
16099423 Nomura M, Nomura N, Yamashita J: Geldanamycin-induced degradation of Chk1 is mediated by proteasome. Biochem Biophys Res Commun. 2005 Sep 30;335(3):900-5.

These results have indicated that degradation of Chk1 by GA was mediated by the ubiquitin-proteasome pathway in U87MG glioblastoma cells.
Co-treatment with GA and cycloheximide (CHX), a protein synthesis inhibitor, induced a decrease of half-life of the Chk1 protein to 3h and resulted in Chk1 down-regulation.
1(0,0,0,1) Details
19561079 Tardito S, Isella C, Medico E, Marchio L, Bevilacqua E, Hatzoglou M, Bussolati O, Franchi-Gazzola R: The thioxotriazole copper (II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19. Epub 2009 Jun 26.

The cytotoxic effects of A0 were associated with inhibition of the ubiquitin-proteasome system and accumulation of ubiquitinylated proteins, in a manner dependent on protein synthesis.
Cycloheximide inhibited the accumulation of ubiquitinylated proteins and hampered A0-induced cell death process.
1(0,0,0,1) Details
15542844 Vega FM, Sevilla A, Lazo PA: p53 Stabilization and accumulation induced by human vaccinia-related kinase 1. Mol Cell Biol. 2004 Dec;24(23):10366-80.


Major mechanisms modulating p53 levels include phosphorylation and interaction of p53 with specific ubiquitin ligases that promote its degradation.
1(0,0,0,1) Details
15735697 Chen C, Sun X, Ran Q, Wilkinson KD, Murphy TJ, Simons JW, Dong JT: Ubiquitin-proteasome degradation of KLF5 transcription factor in cancer and untransformed epithelial cells. Oncogene. 2005 May 5;24(20):3319-27.

1(0,0,0,1) Details
16247473 Saha T, Vardhini D, Tang Y, Katuri V, Jogunoori W, Volpe EA, Haines D, Sidawy A, Zhou X, Gallicano I, Schlegel R, Mishra B, Mishra L: RING finger-dependent ubiquitination by PRAJA is dependent on TGF-beta and potentially defines the functional status of the tumor suppressor ELF. Oncogene. 2006 Feb 2;25(5):693-705.


These studies reveal a mechanism for tumorigenesis whereby defects in adaptor proteins for Smads, such as ELF, can undergo degradation by PRAJA, through the ubiquitin-mediated pathway.
1(0,0,0,1) Details
17912641 Ding WX, Ni HM, Yin XM: Absence of Bax switched MG132-induced apoptosis to non-apoptotic cell death that could be suppressed by transcriptional or translational inhibition. Apoptosis. 2007 Dec;12(12):2233-44.


Targeting to the ubiquitin proteasome degradation pathway has become a promising approach for treating cancer.
1(0,0,0,1) Details
18549879 Sukhthankar M, Yamaguchi K, Lee SH, McEntee MF, Eling TE, Hara Y, Baek SJ: A green tea component suppresses posttranslational expression of basic fibroblast growth factor in colorectal cancer. Gastroenterology. 2008 Jun;134(7):1972-80. Epub 2008 Mar 8.


CONCLUSIONS: The ubiquitin-proteasome degradation pathway contributes significantly to down-regulation of bFGF expression by EGCG.
1(0,0,0,1) Details
15528187 Zhang X, Kolaczkowska A, Devaux F, Panwar SL, Hallstrom TC, Jacq C, Moye-Rowley WS: Transcriptional regulation by Lge1p requires a function independent of its role in histone H2B ubiquitination. J Biol Chem. 2005 Jan 28;280(4):2759-70. Epub 2004 Nov 4.


This ubiquitination requires the presence of the ubiquitin-conjugating enzyme Rad6p and the ubiquitin ligase Bre1p.
1(0,0,0,1) Details
18497737 He F, Doucet JA, Stephens JM: Caspase-mediated degradation of PPARgamma proteins in adipocytes. . Obesity (Silver Spring). 2008 Aug;16(8):1735-41. Epub 2008 May 22.

Previous studies from our laboratory and others have shown that PPARgamma can be ubiquitin modified and targeted to the proteasome for degradation in response to transcriptional activation.
RESULTS: We observed that TNFalpha can induce a caspase-mediated degradation of PPARgamma proteins in the presence of cycloheximide.
1(0,0,0,1) Details
18421014 Meja KK, Rajendrasozhan S, Adenuga D, Biswas SK, Sundar IK, Spooner G, Marwick JA, Chakravarty P, Fletcher D, Whittaker P, Megson IL, Kirkham PA, Rahman I: Curcumin restores corticosteroid function in monocytes exposed to oxidants by maintaining HDAC2. Am J Respir Cell Mol Biol. 2008 Sep;39(3):312-23. Epub 2008 Apr 17.

This decrease in HDAC2 protein expression was reversed by curcumin even in the presence of cycloheximide, a protein synthesis inhibitor.
Biochemical and gene chip analysis indicated that curcumin at concentrations up to 1 muM propagates its effect via antioxidant-independent mechanisms associated with the phosphorylation-ubiquitin-proteasome pathway.
1(0,0,0,1) Details
18339854 Shekhar MP, Gerard B, Pauley RJ, Williams BO, Tait L: Rad6B is a positive regulator of beta-catenin stabilization. Cancer Res. 2008 Mar 15;68(6):1741-50.

Measurement of beta-catenin protein stability by cycloheximide treatment showed that Rad6B silencing specifically decreases the stability of high molecular beta-catenin with minimal effect upon the 90-kDa nascent form.
In vitro ubiquitination assays confirmed that Rad6B mediates beta-catenin polyubiquitination, and ubiquitin chain extensions involve lysine 63 residues that are insensitive to 26S proteasome.
1(0,0,0,1) Details
16094403 Kucharczak JF, Simmons MJ, Duckett CS, Gelinas C: Constitutive proteasome-mediated turnover of Bfl-1/A1 and its processing in response to TNF receptor activation in FL5.12 pro-B cells convert it into a prodeath factor. Cell Death Differ. 2005 Sep;12(9):1225-39.

We show that Bfl-1 undergoes constitutive ubiquitin/proteasome-mediated turnover.
Its anti- versus proapoptotic effect is regulated by two proteolytic events: (1) its constitutive proteasome-mediated turnover and (2) its TNF/cycloheximide (CHX)-induced cleavage by mu-calpain, or a calpain-like activity, coincident with acquisition of a proapoptotic phenotype.
1(0,0,0,1) Details
20087596 Kurepa J, Karangwa C, Duke LS, Smalle JA: Arabidopsis sensitivity to protein synthesis inhibitors depends on 26S proteasome activity. Plant Cell Rep. 2010 Mar;29(3):249-59. Epub 2010 Jan 20.

The 26S proteasome (26SP), the central protease of the ubiquitin-dependent proteolysis pathway, controls the regulated proteolysis of functional proteins and the removal of misfolded and damaged proteins.
We show that the rpt2a-3, rpn10-1 and rpn12a-1 mutants are hypersensitive to the antibiotic hygromycin B, and tolerant to the translation inhibitor cycloheximide (CHX) and herbicide L-phosphinothricin (PPT).
1(0,0,0,1) Details
17550899 Bish RA, Myers MP: Werner helicase-interacting protein 1 binds polyubiquitin via its zinc finger domain. J Biol Chem. 2007 Aug 10;282(32):23184-93. Epub 2007 Jun 5.

Supporting this model, deletion of MGS1, the yeast homolog of WRNIP1, slows the rate of ubiquitin turnover, rendering yeast resistant to cycloheximide.
14(0,0,1,9) Details
18273947 Staszczak M: The role of the ubiquitin-proteasome system in the response of the ligninolytic fungus Trametes versicolor to nitrogen deprivation. Fungal Genet Biol. 2008 Mar;45(3):328-37.

5(0,0,0,5) Details
19366804 Steinkamp MP, O'Mahony OA, Brogley M, Rehman H, Lapensee EW, Dhanasekaran S, Hofer MD, Kuefer R, Chinnaiyan A, Rubin MA, Pienta KJ, Robins DM: Treatment-dependent androgen receptor mutations in prostate cancer exploit multiple mechanisms to evade therapy. Cancer Res. 2009 May 15;69(10):4434-42. Epub 2009 Apr 14.


AR-E255K, mutated in a domain that interacts with an E3 ubiquitin ligase, led to increased protein stability and nuclear localization in the absence of ligand.
1(0,0,0,1) Details
18420039 Garcia-Estrada C, Perez-Pertejo Y, Ordonez D, Balana-Fouce R, Reguera RM: Characterization of the 5' region of the Leishmania infantum LORIEN/MAT2 gene cluster and role of LORIEN flanking regions in post-transcriptional regulation. Biochimie. 2008 Sep;90(9):1325-36. Epub 2008 Mar 28.

LORIEN (encoding a protein that contains a SP-RING/Miz zinc-finger motif present in a group of proteins involved in the Small Ubiquitin-related Modifier -SUMO- conjugation pathway) and MAT2 (encoding the methionine adenosyltransferase -MAT-) genes are arranged as two alternating copies in a head-to-tail configuration, with the LORIEN gene as the first copy of the cluster.
Protein synthesis inhibition by cycloheximide led to an increase in the steady-state levels of LORIEN transcripts only during the promastigote stage, pointing out to the existence of different stage-dependent mechanisms operating on the post-transcriptional regulation of this gene.
1(0,0,0,1) Details
15984167 Tan X, Peng A, Wang YC, Wang Y, Sun QY: Participation of the ubiquitin-proteasome pathway in rat oocyte activation. Zygote. 2005 Feb;13(1):87-95.

ALLN also inhibited the parthenogenetic activation induced by cycloheximide, but had no effect on the formation of pronuclei in activated eggs.
4(0,0,0,4) Details
15545831 Chang C, Chang AY, Chan SH: De novo synthesis of ubiquitin carboxyl-terminal hydrolase isozyme l1 in rostral ventrolateral medulla is crucial to survival during mevinphos intoxication. Shock. 2004 Dec;22(6):575-81.

Ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1) is a deubiquitinating enzyme that is responsible for making ubiquitin, which is required to target proteins for degradation by the ubiquitin-proteasome pathway in neurons, available.
The increase in UCH-L1 level was significantly blunted on pretreatment with bilateral microinjection into the RVLM of a transcription inhibitor, actinomycin D (5 nmol), or a translation inhibitor, cycloheximide (20 nmol).
4(0,0,0,4) Details
18436532 Kohlmann S, Schafer A, Wolf DH: Ubiquitin ligase Hul5 is required for fragment-specific substrate degradation in endoplasmic reticulum-associated degradation. J Biol Chem. 2008 Jun 13;283(24):16374-83. Epub 2008 Apr 24.

3(0,0,0,3) Details
19741096 Yonashiro R, Sugiura A, Miyachi M, Fukuda T, Matsushita N, Inatome R, Ogata Y, Suzuki T, Dohmae N, Yanagi S: Mitochondrial ubiquitin ligase MITOL ubiquitinates mutant SOD1 and attenuates mutant SOD1-induced reactive oxygen species generation. Mol Biol Cell. 2009 Nov;20(21):4524-30. Epub 2009 Sep 9.

Cycloheximide-chase assay in the Neuro2a cells indicated that MITOL overexpression promoted mSOD1 degradation and suppressed both the mitochondrial accumulation of mSOD1 and mSOD1-induced reactive oxygen species (ROS) generation.
3(0,0,0,3) Details
15814588 Kuang PP, Goldstein RH: Regulation of elastin gene transcription by proteasome dysfunction. Am J Physiol Cell Physiol. 2005 Sep;289(3):C766-73. Epub 2005 Apr 6.

We previously found that the downregulation of elastin gene transcription by IL-1beta is mediated via activation of NF-kappaB and CCAAT/enhancer binding protein (C/EBP) beta, both targets of the ubiquitin-proteasome pathway.
Addition of cycloheximide blocked these increases and the downregulation of elastin mRNA by MG-132.
3(0,0,0,3) Details
16227590 Pluquet O, Qu LK, Baltzis D, Koromilas AE: Endoplasmic reticulum stress accelerates p53 degradation by the cooperative actions of Hdm2 and glycogen synthase kinase 3beta. Mol Cell Biol. 2005 Nov;25(21):9392-405.


We demonstrate here that the E3 ubiquitin-ligase Hdm2 is essential for the nucleocytoplasmic transport and proteasome-dependent degradation of p53 in ER-stressed cells.
1(0,0,0,1) Details
17267405 Stribinskis V, Ramos KS: Rpm2p, a protein subunit of mitochondrial RNase P, physically and genetically interacts with cytoplasmic processing bodies. Nucleic Acids Res. 2007;35(4):1301-11. Epub 2007 Jan 31.

When overexpressed, GFP-Rpm2p does not impact the number and size of P bodies; however, it prevents their disappearance when translation elongation is inhibited by cycloheximide.
The stabilization of P bodies by Rpm2p may occur through reduced protein degradation since GFP-Rpm2p expressing cells have lower levels of ubiquitin.
1(0,0,0,1) Details
18775696 Tsai KW, Tseng HC, Lin WC: Two wobble-splicing events affect ING4 protein subnuclear localization and degradation. Exp Cell Res. 2008 Oct 15;314(17):3130-41. Epub 2008 Aug 15.


We also observed that ING4 is degraded through the ubiquitin-proteasome pathway and that it is subjected to N-terminal ubiquitination.
1(0,0,0,1) Details
18784257 Chen G, Huang H, Frohlich O, Yang Y, Klein JD, Price SR, Sands JM: MDM2 E3 ubiquitin ligase mediates UT-A1 urea transporter ubiquitination and degradation. Am J Physiol Renal Physiol. 2008 Nov;295(5):F1528-34. Epub 2008 Sep 10.

3(0,0,0,3) Details
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.

3(0,0,0,3) Details
16849335 Cottrell GS, Padilla B, Pikios S, Roosterman D, Steinhoff M, Gehringer D, Grady EF, Bunnett NW: Ubiquitin-dependent down-regulation of the neurokinin-1 receptor. . J Biol Chem. 2006 Sep 22;281(38):27773-83. Epub 2006 Jul 17.

Resensitization occurred after 16 h, and cycloheximide prevented resensitization, implicating new receptor synthesis.
2(0,0,0,2) Details
19135226 Li F, Li M, Ke W, Ji Y, Bian X, Yan X: Identification of the immediate-early genes of white spot syndrome virus. Virology. 2009 Mar 1;385(1):267-74. Epub 2009 Jan 8.

Here we screened white spot syndrome virus (WSSV) IE genes with cycloheximide (CHX)-treated primary culture of crayfish hemocyte and a WSSV genome tiling microarray.
The 16 identified IE proteins contain four proteins (wsv051, wsv069, wsv100, wsv079) with transcription activity, one (wsv083) with Ser/Thr kinase domain and one (wsv249) previously described to function as an ubiquitin E3 ligase.
1(0,0,0,1) Details
17475922 Egozi D, Shapira M, Paor G, Ben-Izhak O, Skorecki K, Hershko DD: Regulation of the cell cycle inhibitor p27 and its ubiquitin ligase Skp2 in differentiation of human embryonic stem cells. FASEB J. 2007 Sep;21(11):2807-17. Epub 2007 May 2.

2(0,0,0,2) Details
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 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.
2(0,0,0,2) Details
19137541 Rizzi F, Caccamo AE, Belloni L, Bettuzzi S: Clusterin is a short half-life, poly-ubiquitinated protein, which controls the fate of prostate cancer cells. J Cell Physiol. 2009 May;219(2):314-23.

Inhibition of protein synthesis by cycloheximide showed that CLU half-life is less than 2 h.
Quite surprisingly, we also found that the turnover of CLU protein is very rapid and tightly regulated by ubiquitin-proteasome mediated degradation.
1(0,0,0,1) Details
16503970 Alao JP, Gamble SC, Stavropoulou AV, Pomeranz KM, Lam EW, Coombes RC, Vigushin DM: The cyclin D1 proto-oncogene is sequestered in the cytoplasm of mammalian cancer cell lines. Mol Cancer. 2006 Feb 17;5:7.


We have demonstrated previously, that TSA induces the ubiquitin-dependent degradation of cyclin D1 in MCF-7 breast cancer cells.
1(0,0,0,1) Details
19074853 Feng Q, Sekula D, Guo Y, Liu X, Black CC, Galimberti F, Shah SJ, Sempere LF, Memoli V, Andersen JB, Hassel BA, Dragnev K, Dmitrovsky E: UBE1L causes lung cancer growth suppression by targeting cyclin D1. . Mol Cancer Ther. 2008 Dec;7(12):3780-8.

UBE1L is the E1-like ubiquitin-activating enzyme for the IFN-stimulated gene, 15-kDa protein (ISG15).
Cycloheximide treatment augmented this cyclin D1 protein instability.
2(0,0,0,2) Details
19164805 Rutledge AC, Qiu W, Zhang R, Kohen-Avramoglu R, Nemat-Gorgani N, Adeli K: Mechanisms targeting apolipoprotein B100 to proteasomal degradation: evidence that degradation is initiated by BiP binding at the N terminus and the formation of a p97 complex at the C terminus. Arterioscler Thromb Vasc Biol. 2009 Apr;29(4):579-85. Epub 2009 Jan 22.


OBJECTIVE: In lipid-poor states, the ubiquitin-proteasomal pathway rapidly degrades misfolded apolipoprotein B100 (apoB) cotranslationally, although the mechanism of delivery from the ER to cytosolic proteasomes is poorly understood.
2(0,0,0,2) Details
16234850 Abu-Farha M, Niles J, Willmore WG: Erythroid-specific 5-aminolevulinate synthase protein is stabilized by low oxygen and proteasomal inhibition. Biochem Cell Biol. 2005 Oct;83(5):620-30.

The present study provides evidence that ALAS2 is broken down under normoxic conditions by the proteasome and that the prolyl-4-hydroxylase/vHL E3 ubiquitin ligase pathway may be involved.
We examined protein turnover of ALAS2 in the presence of cycloheximide in K562 cells.
1(0,0,0,1) Details
15919663 Dulloo I, Sabapathy K: Transactivation-dependent and -independent regulation of p73 stability. J Biol Chem. 2005 Aug 5;280(31):28203-14. Epub 2005 May 26.


Finally, we have identified the regions between amino acids 56 and 248 of p73 as being the region required for p73-mediated and for ubiquitin-mediated degradation.
1(0,0,0,1) Details
17535899 Fu NY, Sukumaran SK, Yu VC: Inhibition of ubiquitin-mediated degradation of MOAP-1 by apoptotic stimuli promotes Bax function in mitochondria. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10051-6. Epub 2007 May 29.

Mitochondria depleted of short-lived proteins by cycloheximide (CHX) become resistant to Bax-mediated cytochrome c release.
2(0,0,0,2) Details
18229456 Shenkman M, Tolchinsky S, Lederkremer GZ: ER stress induces alternative nonproteasomal degradation of ER proteins but not of cytosolic ones. Cell Stress Chaperones. 2007 Winter;12(4):373-83.

At later stages it upregulates components of ER-associated degradation (ERAD) and of the ubiquitin/proteasome system, which targets ER as well as cytosolic proteins for disposal.
To mimic the initial inhibition of translation during UPR, we incubated cells with cycloheximide.
2(0,0,0,2) Details
15684817 Liu M, Hummer BT, Li X, Hassel BA: Camptothecin induces the ubiquitin-like protein, ISG15, and enhances ISG15 conjugation in response to interferon. J Interferon Cytokine Res. 2004 Nov;24(11):647-54.

2(0,0,0,2) Details
18223147 Chung HS, Koo AJ, Gao X, Jayanty S, Thines B, Jones AD, Howe GA: Regulation and function of Arabidopsis JASMONATE ZIM-domain genes in response to wounding and herbivory. Plant Physiol. 2008 Mar;146(3):952-64. Epub 2008 Jan 25.

Recent studies indicate that JA-Ile promotes the degradation of JASMONATE ZIM-domain (JAZ) transcriptional repressors through the activity of the E (3) ubiquitin-ligase SCF (COI1).
Experiments performed with the protein synthesis inhibitor cycloheximide provided evidence that JAZs, MYC2, and genes encoding several JA biosynthetic enzymes are primary response genes whose expression is derepressed upon COI1-dependent turnover of a labile repressor protein (s).
1(0,0,0,1) Details
15574338 Chen X, Chi Y, Bloecher A, Aebersold R, Clurman BE, Roberts JM: N-acetylation and ubiquitin-independent proteasomal degradation of p21 (Cip1). Mol Cell. 2004 Dec 3;16(5):839-47.

1(0,0,0,1) Details
19769966 Tominaga K, Tominaga E, Ausserlechner MJ, Pereira-Smith OM: The cell senescence inducing gene product MORF4 is regulated by degradation via the ubiquitin/proteasome pathway. Exp Cell Res. 2010 Jan 1;316(1):92-102. Epub 2009 Sep 19.

1(0,0,0,1) Details
16492674 Berry FB, Mirzayans F, Walter MA: Regulation of FOXC1 stability and transcriptional activity by an epidermal growth factor-activated mitogen-activated protein kinase signaling cascade. J Biol Chem. 2006 Apr 14;281(15):10098-104. Epub 2006 Feb 21.


Finally, we have demonstrated that FOXC1 is targeted to the ubiquitin 26 S proteasomal degradation pathway and that amino acid residues 367-553, which include the C-terminal transactivation domain of FOXC1, are essential for ubiquitin incorporation and proteolysis.
1(0,0,0,1) Details
16177134 Kwapisz M, Cholbinski P, Hopper AK, Rousset JP, Zoladek T: Rsp5 ubiquitin ligase modulates translation accuracy in yeast Saccharomyces cerevisiae. RNA. 2005 Nov;11(11):1710-8. Epub 2005 Sep 21.

2(0,0,0,2) Details
17018280 Hanna J, Hathaway NA, Tone Y, Crosas B, Elsasser S, Kirkpatrick DS, Leggett DS, Gygi SP, King RW, Finley D: Deubiquitinating enzyme Ubp6 functions noncatalytically to delay proteasomal degradation. Cell. 2006 Oct 6;127(1):99-111.


Ubiquitin chains serve as a recognition motif for the proteasome, a multisubunit protease, which degrades its substrates into polypeptides while releasing ubiquitin for reuse.
2(0,0,0,2) Details
15966900 Minegishi N, Suzuki N, Kawatani Y, Shimizu R, Yamamoto M: Rapid turnover of GATA-2 via ubiquitin-proteasome protein degradation pathway. Genes Cells. 2005 Jul;10(7):693-704.

In P815 cells, the half-life of endogenous GATA-2 was found to be as short as 30 min after cycloheximide treatment.
2(0,0,0,2) Details
19602254 Bangiyeva V, Rosenbloom A, Alexander AE, Isanova B, Popko T, Schoenfeld AR: Differences in regulation of tight junctions and cell morphology between VHL mutations from disease subtypes. BMC Cancer. 2009 Jul 14;9:229.


The VHL gene product is part of an ubiquitin E3 ligase complex and hypoxia-inducible factor alpha (HIF-alpha) is a key substrate, although additional VHL functions have been described.
1(0,0,0,1) Details
17373649 Li JP, Yang JL: Cyclin B1 proteolysis via p38 MAPK signaling participates in G2 checkpoint elicited by arsenite. J Cell Physiol. 2007 Aug;212(2):481-8.


This rapid destruction of cyclin B1 was mediated via the ubiquitin-proteasome pathway probably in a Cdc20 and Cdh1 independent mechanism.
1(0,0,0,1) Details
19590044 Vignier N, Schlossarek S, Fraysse B, Mearini G, Kramer E, Pointu H, Mougenot N, Guiard J, Reimer R, Hohenberg H, Schwartz K, Vernet M, Eschenhagen T, Carrier L: Nonsense-mediated mRNA decay and ubiquitin-proteasome system regulate cardiac myosin-binding protein C mutant levels in cardiomyopathic mice. Circ Res. 2009 Jul 31;105(3):239-48. Epub 2009 Jul 9.

Inhibition of nonsense-mediated mRNA decay in cultured cardiac myocytes or in vivo with emetine or cycloheximide increased the level of nonsense mRNAs severalfold but not of the other mRNAs.
2(0,0,0,2) Details
17711404 Chan SC, Lin SC, Li P: Regulation of Cidea protein stability by the ubiquitin-mediated proteasomal degradation pathway. Biochem J. 2007 Dec 1;408(2):259-66.

In the present study we show that Cidea is a short-lived protein as measured by cycloheximide-based protein chase experiments in different cell lines or in differentiated brown adipocytes.
2(0,0,0,2) Details
19880452 Jabbour M, Campbell EM, Fares H, Lybarger L: Discrete domains of MARCH1 mediate its localization, functional interactions, and posttranscriptional control of expression. J Immunol. 2009 Nov 15;183(10):6500-12. Epub 2009 Oct 30.


MARCH1 (membrane-associated RING-CH), a newly identified ubiquitin E3 ligase expressed in APCs, ubiquitinates MHC class II, thereby reducing its surface expression.
1(0,0,0,1) Details
17692850 Scherer GF, Zahn M, Callis J, Jones AM: A role for phospholipase A in auxin-regulated gene expression. FEBS Lett. 2007 Sep 4;581(22):4205-11. Epub 2007 Aug 3.

In the presence of cycloheximide and excluding synthesis of IAA1:luciferase, ETYA had no apparent effect on degradation rates of IAA1, either with or without exogenous auxin.
Factors that bind to the auxin response elements of the DR5 promoter and thereby regulate gene expression are regulated by a set of proteins such as Aux/IAA1 whose abundances are, in part, under control of E3 ubiquitin ligase SCF complexes.
1(0,0,0,1) Details
20305002 Kingsbury JM, McCusker JH: Homoserine toxicity in Saccharomyces cerevisiae and Candida albicans homoserine kinase (thr1{Delta}) mutants. Eukaryot Cell. 2010 Mar 19.

Homoserine-mediated lethality of thr1Delta mutants is blocked by cycloheximide, consistent with a role for protein synthesis in this lethality.
We identified various proteasome and ubiquitin pathway components that either when mutated or present in high copy, suppressed the thr1Delta mutant homoserine toxicity.
2(0,0,0,2) Details
18303026 Tatematsu K, Yoshimoto N, Okajima T, Tanizawa K, Kuroda S: Identification of ubiquitin ligase activity of RBCK1 and its inhibition by splice variant RBCK2 and protein kinase Cbeta. J Biol Chem. 2008 Apr 25;283(17):11575-85. Epub 2008 Feb 25.

2(0,0,0,2) Details
19591933 Mishra A, Godavarthi SK, Jana NR: UBE3A/E6-AP regulates cell proliferation by promoting proteasomal degradation of p27. Neurobiol Dis. 2009 Oct;36(1):26-34. Epub 2009 Jul 8.


The UBE3A/E6-AP is known to function both as an E3 ubiquitin ligase of the ubiquitin proteasome system and as a transcriptional coactivator.
1(0,0,0,1) Details
17338678 Shenkman M, Tolchinsky S, Kondratyev M, Lederkremer GZ: Transient arrest in proteasomal degradation during inhibition of translation in the unfolded protein response. Biochem J. 2007 Jun 15;404(3):509-16.


Consistent with this, protein synthesis inhibitors blocked ubiquitin/proteasomal degradation.
1(0,0,0,1) Details
16359394 Shen H, Moon J, Huq E: PIF1 is regulated by light-mediated degradation through the ubiquitin-26S proteasome pathway to optimize photomorphogenesis of seedlings in Arabidopsis. Plant J. 2005 Dec;44(6):1023-35.

Further, de novo protein synthesis is not required for degradation of PIF1, as the presence of cycloheximide does not prevent degradation of PIF1 in the light.
2(0,0,0,2) 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.

2(0,0,0,2) Details
17395740 Kaniuk NA, Kiraly M, Bates H, Vranic M, Volchuk A, Brumell JH: Ubiquitinated-protein aggregates form in pancreatic beta-cells during diabetes-induced oxidative stress and are regulated by autophagy. Diabetes. 2007 Apr;56(4):930-9.

Diabetes-induced oxidative stress can lead to protein misfolding and degradation by the ubiquitin-proteasome system.
However, cycloheximide (which blocks translation) did not impair Ub-protein aggregate formation at high glucose levels, suggesting that long-lived proteins are targeted to these structures.
1(0,0,0,1) Details
19663814 Choi C, Lee J, Lim C, Jang D, Choe J: The DOUBLETIME protein kinase regulates phosphorylation of the Drosophila PDP1epsilon. J Neurochem. 2009 Oct;111(1):264-73. Epub 2009 Aug 5.


We also demonstrate that DBT interacts with PDP1epsilon and promotes its degradation by the ubiquitin-proteasome pathway in cultured cells.
1(0,0,0,1) Details
17363499 Ding WX, Ni HM, Chen X, Yu J, Zhang L, Yin XM: A coordinated action of Bax, PUMA, and p53 promotes MG132-induced mitochondria activation and apoptosis in colon cancer cells. Mol Cancer Ther. 2007 Mar;6(3):1062-9.

Consistently, inhibition of translation by cycloheximide could also effectively abolish the accumulation of p53 and PUMA and suppress MG132-induced Bax activation and apoptosis.
Targeting the ubiquitin-proteasome degradation pathway has become a promising approach for cancer therapy.
1(0,0,0,1) Details
17157811 Shen Y, Ballar P, Apostolou A, Doong H, Fang S: ER stress differentially regulates the stabilities of ERAD ubiquitin ligases and their substrates. Biochem Biophys Res Commun. 2007 Jan 26;352(4):919-24. Epub 2006 Dec 4.

Importantly, ER stress could increase ERAD even when new protein synthesis was inhibited by cycloheximide.
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16925598 Subramanian C, Woo J, Cai X, Xu X, Servick S, Johnson CH, Nebenfuhr A, von Arnim AG: A suite of tools and application notes for in vivo protein interaction assays using bioluminescence resonance energy transfer (BRET). Plant J. 2006 Oct;48(1):138-52. Epub 2006 Aug 22.

Working in stably transformed Arabidopsis or tobacco, we then detected BRET between three pairs of candidate interaction partners: dimerization of the E3 ubiquitin ligase COP1, interaction between COP1 and the B-box protein STH, and interaction between the light regulatory bZip transcription factors HY5 and HYH.
Finally, we show that Renilla luciferase may serve as a reporter of protein stability in a cycloheximide chase assay.
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17310067 Cottrell GS, Padilla B, Pikios S, Roosterman D, Steinhoff M, Grady EF, Bunnett NW: Post-endocytic sorting of calcitonin receptor-like receptor and receptor activity-modifying protein 1. J Biol Chem. 2007 Apr 20;282(16):12260-71. Epub 2007 Feb 19.

After sustained stimulation, CLR and RAMP1 traffic from endosomes to lysosomes by ubiquitin-independent mechanisms, where they are degraded at different rates.
Cycloheximide did not affect resensitization, but bafilomycin A (1), an inhibitor of vacuolar H (+)-ATPases, abolished resensitization.
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18154321 Lurie LJ, Boyer ME, Grass JA, Bresnick EH: Differential GATA factor stabilities: implications for chromatin occupancy by structurally similar transcription factors. Biochemistry. 2008 Jan 22;47(3):859-69. Epub 2007 Dec 23.


We used two independent assays to demonstrate that GATA-1 is considerably more stable than GATA-2 in multiple cellular contexts, even though both factors are subject to degradation via the ubiquitin-proteasome system.
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