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• W1984948285 endingPage "139" @default.
• W1984948285 startingPage "130" @default.
• W1984948285 abstract "DNA damage results in an increase in P53 levels, which is required to initiate a P53-mediated cell cycle arrest and/or apoptosis. P53 and MDM-2 form a feedback control loop: while P53 can transactivate the MDM-2 gene, high levels of MDM-2 inhibit P53 transactivation as well as promote rapid degradation of P53. In the present study, we investigated the interaction between endogenous MDM-2 and P53 following UV-induced DNA damage in an MDM-2 overexpression cell line. A human osteosarcoma cell line (OsACL, which contains wild-type P53 and overexpresses MDM-2 protein) was used in this study. Here we show that following UV treatment, P53 levels increased in the OsACL cells despite the presence of high-level endogenous MDM-2; however, CAT assays using a P53 reporter system revealed that this P53 was transcriptionally inactive. Although P53 transactivation was inhibited, MDM-2 levels rose markedly following UV irradiation. Northern blot analysis revealed that the increase in MDM-2 protein levels was a result of increased levels of MDM-2 mRNA, possibly due to increased transcription. Cell cycle analysis revealed that OsACL cells were markedly resistant to UV-induced apoptosis. Transfection of OsACL cells with an anti-sense MDM-2 plasmid dowregulated MDM-2 expression and increased UV-induced apoptosis. In conclusion, MDM-2 overexpression can block UV-induced cell cycle arrest and apoptosis by inhibiting P53 transcriptional activity. Furthermore, increased expression of MDM-2 in OsACL cells following UV irradiation appears to be related to P53-independent mechanisms." @default.
• W1984948285 created "2016-06-24" @default.
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• W1984948285 date "2003-01-01" @default.
• W1984948285 modified "2023-09-25" @default.
• W1984948285 title "Increased <i>mdm-2</i> Expression in a <i>p53</i>-Independent Manner Blocks UV-Induced Cell Cycle Arrest and Apoptosis in Human Osteosarcoma Cells" @default.
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• W1984948285 doi "https://doi.org/10.1159/000073842" @default.
• W1984948285 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/14610316" @default.
• W1984948285 hasPublicationYear "2003" @default.
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