دورية أكاديمية
Ascochlorin activates p53 in a manner distinct from DNA damaging agents
| العنوان: | Ascochlorin activates p53 in a manner distinct from DNA damaging agents |
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| المساهمون: | Ji-Hak Jeong, Hiroo Nakajima, Junji Magae, Chiharu Furukawa, Keiko Taki, Kensuke Otsuka, Masanori Tomita, In-Seon Lee, Cheorl-Ho Kim, Hyeun-Wook Chang, Kwan-Sik Min, Kwang-Kyun Park, Kwan-Kyu Park, Young-Chae Chang, Park, Kwang Kyun |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Adenosine Triphosphate/metabolism, Alkenes/pharmacology, Antibiotics, Antineoplastic/pharmacology, Ataxia Telangiectasia Mutated Proteins, Blotting, Western, Bone Neoplasms/genetics, Bone Neoplasms/metabolism, Bone Neoplasms/pathology, Cell Cycle Proteins/genetics, Cell Cycle Proteins/metabolism, Cell Line, Tumor, Cell Respiration/drug effects, Checkpoint Kinase 1, Comet Assay, DNA Breaks, Double-Stranded, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Electrophoretic Mobility Shift Assay, Fluorescent Antibody Technique, Humans, Mitochondria/drug effects, Mitochondria/metabolism, Osteosarcoma/genetics, Osteosarcoma/metabolism, Osteosarcoma/pathology, Phenols/pharmacology |
| الوصف: | Ascochlorin, a prenylphenol antitumor antibiotic, profoundly increases the expression of endogenous p53 by increasing protein stability in the human osteosarcoma cells and human colon cancer cells. Ascochlorin also increases DNA binding activity to the p53 consensus sequence in nuclear extract and enhances transcription of p53 downstream targets. Ascochlorin specifically induces p53 phosphorylation at ser 392 without affecting ser 15 or 20, whereas DNA damaging agents typically phosphorylate these serines. Moreover, ascochlorin does not induce phosphorylation of ATM and CHK1, an established substrate of ATR that is activated by genotoxins, nor does it increase DNA strand break, as confirmed by comet assay. The structure-activity relationship suggests that p53 activation by ascochlorin is related to inhibition of mitochondrial respiration, which is further supported by the observation that respiratory inhibitors activate p53 in a manner similar to ascochlorin. These results suggest that ascochlorin, through the inhibition of mitochondrial respiration, activates p53 through a mechanism distinct from genotoxins. ; open |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 2797~2803 |
| اللغة: | unknown |
| تدمد: | 0020-7136 1097-0215 |
| العلاقة: | INTERNATIONAL JOURNAL OF CANCER; J01092; OAK-2009-01972; https://ir.ymlib.yonsei.ac.kr/handle/22282913/105312Test; T200903705; INTERNATIONAL JOURNAL OF CANCER, Vol.124(12) : 2797-2803, 2009 |
| DOI: | 10.1002/ijc.24259 |
| DOI: | 10.1002/ijc.24259/abstract |
| الإتاحة: | https://doi.org/10.1002/ijc.24259Test https://ir.ymlib.yonsei.ac.kr/handle/22282913/105312Test |
| حقوق: | CC BY-NC-ND 2.0 KR ; https://creativecommons.org/licenses/by-nc-nd/2.0/krTest/ |
| رقم الانضمام: | edsbas.3A18332E |
| قاعدة البيانات: | BASE |
| تدمد: | 00207136 10970215 |
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| DOI: | 10.1002/ijc.24259 |