Cited 26 times in
Inhibition of AP-1 transcription activator induces myc-dependent apoptosis in HL60 cells
DC Field | Value | Language |
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dc.contributor.author | 박세연 | - |
dc.date.accessioned | 2015-07-14T16:38:56Z | - |
dc.date.available | 2015-07-14T16:38:56Z | - |
dc.date.issued | 2004 | - |
dc.identifier.issn | 0730-2312 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/111310 | - |
dc.description.abstract | Transcriptional activation of AP-1 is intricately involved in cell proliferation and transformation. The natural product, nordihydroguaiaretic acid (NDGA) shows an inhibitory effect on the binding of jun/AP-1 protein to the AP-1 site in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated HL60 cells. The NDGA inhibits the auto-regulated de novo synthesis of c-jun mRNA in TPA-stimulated HL60 cells. Our data also determine that this compound induces proliferation inhibition and apoptosis in human leukemia HL60 cells. To obtain information on the functional role of the AP-1 inhibition by NDGA in apoptosis signaling, the effects of pharmacological inhibition of AP-1 binding on c-myc, p53, and bax protein level were determined. Our results indicate that treatment of cells with NDGA enhances c-myc, p53, and bax protein levels. To rule out the possibility that NDGA will induce apoptosis because of the effects on proteins other than AP-1, we investigated the effect of another AP-1 inhibitor, SP600125, which is specific to Jun-N-terminal kinase. SP600125 decreased not only the phosphorylation level of jun protein but also AP-1/DNA binding activity. Also, apoptosis was observed to be induced by SP600125, concomitant with the increase in c-myc, p53, and bax protein level. In addition, apoptosis induced by both AP-1 inhibitors was accompanied by the activation of a downstream apoptotic cascade such as caspase 9, caspase 3, and poly[ADP-ribose]polymerase (PARP). When the cells were treated with NDGA or SP600125 in the presence of antisense c-myc oligonucleotides, apoptosis was not observed and an increase of c-myc, p53, and bax proteins was not manifested. All these results show that the inhibition of the transcription factor AP-1 action is related with either the drug-induced apoptosis or the drug toxicity of the HL60 cells. The apoptosis induced by AP-1 inhibition may be dependent on c-myc protein levels suggesting that the c-myc protein induces apoptosis at a low level of AP-1 binding activity. Altogether, our findings suggest that the presence of the AP-1 signal acts as a survival factor that determines the outcome of myc-induced proliferation or apoptosis. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 973~986 | - |
dc.relation.isPartOf | JOURNAL OF CELLULAR BIOCHEMISTRY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Inhibition of AP-1 transcription activator induces myc-dependent apoptosis in HL60 cells | - |
dc.type | Article | - |
dc.contributor.college | Researcher Institutes (부설 연구소) | - |
dc.contributor.department | Anesthesia and Pain Research Institute (마취통증의학연구소) | - |
dc.contributor.googleauthor | Seyeon Park | - |
dc.contributor.googleauthor | Eun-Ryeong Hahm | - |
dc.contributor.googleauthor | Chul-Hak Yang | - |
dc.contributor.googleauthor | Dug-Keun Lee | - |
dc.identifier.doi | 10.1002/jcb.10768 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.relation.journalcode | J01303 | - |
dc.identifier.eissn | 1097-4644 | - |
dc.identifier.url | http://onlinelibrary.wiley.com/doi/10.1002/jcb.10768/abstract | - |
dc.subject.keyword | jun/AP‐1 | - |
dc.subject.keyword | inhibitor | - |
dc.subject.keyword | HL60 cell | - |
dc.subject.keyword | apoptosis | - |
dc.subject.keyword | c‐myc | - |
dc.contributor.alternativeName | Park, Se Yeon | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 91 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 973 | - |
dc.citation.endPage | 986 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CELLULAR BIOCHEMISTRY, Vol.91(5) : 973-986, 2004 | - |
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