Protein Information

Name AP 1 (protein family or complex)
Synonyms AP 1; AP 1 complex; AP1; Adapter related protein complex 1

Compound Information

Name cycloheximide
CAS

Reference List

PubMed Abstract RScore(About this table)
17641275 Kwakkel J, Wiersinga WM, Boelen A: Interleukin-1beta modulates endogenous thyroid hormone receptor alpha gene transcription in liver cells. J Endocrinol. 2007 Aug;194(2):257-65.

Cycloheximide experiments showed that the decreased promoter activity is independent of de novo protein synthesis and therefore most likely due to posttranslational modifications such as phosphorylation or subcellular relocalization.
Proinflammatory cytokine induction leads to activation of the inflammatory pathways nuclear factor (NF) kappaB and activator protein (AP)-1.
2(0,0,0,2) Details
15598649 Kyttala A, Yliannala K, Schu P, Jalanko A, Luzio JP: AP-1 and AP-3 facilitate lysosomal targeting of Batten disease protein CLN3 via its dileucine motif. J Biol Chem. 2005 Mar 18;280(11):10277-83. Epub 2004 Dec 13.

2(0,0,0,2) Details
17941091 Chiu YC, Huang TH, Fu WM, Yang RS, Tang CH: Ultrasound stimulates MMP-13 expression through p38 and JNK pathway in osteoblasts. J Cell Physiol. 2008 May;215(2):356-65.

Cycloheximide (an inhibitor of protein translocation) and actinomycin D (an inhibitor of gene transcription) did not inhibit the MMP-13, c-Fos, and c-Jun mRNA expression, suggesting that such expression does not require de novo protein synthesis and not change their stabilities. p38 inhibitor, SB203580 or JNK inhibitor, SP600125 but not ERK inhibitor, PD98059 attenuated the US-induced MMP-13, c-Fos, and c-Jun expression; these results were further substantiated by transfecting with the dominant negative mutants of p38 or JNK.
The binding of c-Fos and c-Jun to the AP-1 element on the MMP-13 promoter and the enhancement of AP-1 luciferase activity was enhanced by US stimulation.
1(0,0,0,1) Details
15569826 Furst R, Brueckl C, Kuebler WM, Zahler S, Krotz F, Gorlach A, Vollmar AM, Kiemer AK: Atrial natriuretic peptide induces mitogen-activated protein kinase phosphatase-1 in human endothelial cells via Rac1 and NAD (P) H oxidase/Nox2-activation. Circ Res. 2005 Jan 7;96(1):43-53. Epub 2004 Nov 29.


MKP-1 induction was shown to depend on activation of the transcription factor activator protein-1 (AP-1) by using electrophoretic mobility shift assay and AP-1 decoys.
1(0,0,0,1) Details
16158421 Jin HO, Park IC, An S, Lee HC, Woo SH, Hong YJ, Lee SJ, Park MJ, Yoo DH, Rhee CH, Hong SI: Up-regulation of Bak and Bim via JNK downstream pathway in the response to nitric oxide in human glioblastoma cells. J Cell Physiol. 2006 Feb;206(2):477-86.

Treatment with SNAP resulted in sustained activation of JNK and its downstream pathway, c-Jun/AP-1.
In addition, de novo protein synthesis was required for the initiation of apoptosis in that the protein synthesis inhibitor, cycloheximide (CHX), inhibited NO-induced apoptotic cell death as well as up-regulation of Bak and Bim.
1(0,0,0,1) Details
17573545 Periz G, Dharia D, Miller SH, Keller LR: Flagellar elongation and gene expression in Chlamydomonas reinhardtii. Eukaryot Cell. 2007 Aug;6(8):1411-20. Epub 2007 Jun 15.

Li (+)-induced flagellar gene expression occurs in cells pretreated with cycloheximide, suggesting that the abundance change is a response that does not require new protein synthesis.
Deletion analysis of the flagellar alpha1-tubulin gene promoter showed that sequences necessary for Li (+)-induced expression differed from those for acid shock induction and contain a consensus binding site for CREB/ATF and AP-1 transcription factors.
1(0,0,0,1) Details
18854426 Gu JQ, Ikuyama S, Wei P, Fan B, Oyama J, Inoguchi T, Nishimura J: Pycnogenol, an extract from French maritime pine, suppresses Toll-like receptor 4-mediated expression of adipose differentiation-related protein in macrophages. Am J Physiol Endocrinol Metab. 2008 Dec;295(6):E1390-400. Epub 2008 Oct 14.

Actinomycin D almost completely abolished the LPS effect, whereas cycloheximide decreased the expression at 12 h, indicating that the LPS-induced ADRP expression was stimulated at the transcriptional level and was also mediated by new protein synthesis.
LPS enhanced the ADRP promoter activity, in part, by stimulating activator protein (AP)-1 binding to the Ets/AP-1 element.
1(0,0,0,1) Details
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.
1(0,0,0,1) Details
16325375 Zhang L, Tie Y, Tian C, Xing G, Song Y, Zhu Y, Sun Z, He F: CKIP-1 recruits nuclear ATM partially to the plasma membrane through interaction with ATM. Cell Signal. 2006 Sep;18(9):1386-95. Epub 2005 Dec 1.

More recently, we showed that CKIP-1 regulated AP-1 activity and promoted apoptosis via caspase-3-dependent cleavage and translocation.
Here, we report that overexpression of CKIP-1 in SK-BR-3 breast cancer cells prevents p53 degradation induced by cycloheximide treatment through increase of p53 N-terminal Ser-15 phosphorylation level.
1(0,0,0,1) Details
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.
0(0,0,0,0) Details
16146692 Yasuda T, Kanno M, Kawamoto M, Yuge O, Ninomiya Y: Suppression of inducible nitric oxide synthase and cyclooxygenase-2 gene expression by 22 (R)-hydroxycholesterol requires de novo protein synthesis in activated macrophages. J Steroid Biochem Mol Biol. 2005 Dec;97(4):376-83. Epub 2005 Sep 16.


Furthermore iNOS and COX-2 mRNA suppression by 22R-HC was diminished by cellular treatment with cycloheximide.
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17160021 Portal MM, Ferrero GO, Caputto BL: N-Terminal c-Fos tyrosine phosphorylation regulates c-Fos/ER association and c-Fos-dependent phospholipid synthesis activation. Oncogene. 2007 May 24;26(24):3551-8. Epub 2006 Dec 11.


c-Fos dephosphorylated on tyrosine (c-Fos), a component of the activator protein-1 (AP-1) family of transcription factors, is expressed at very low levels in resting cells.
2(0,0,0,2) Details
16274708 Heurtaux T, Benani A, Moulin D, Muller N, Netter P, Minn A: Induction of UGT1A6 isoform by inflammatory conditions in rat astrocytes. . Neuropharmacology. 2006 Mar;50(3):317-28. Epub 2005 Nov 7.

Moreover, gel shift assay revealed increased activator protein-1 (AP-1) binding activity after LPS treatment.
Moreover, this endotoxin-induced increase in UGT1A6 expression level was blocked by actinomycin D and cycloheximide, indicating the requirement for RNA and protein synthesis.
2(0,0,0,2) Details