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DNA损伤会增加野生型p53人类细胞中MDM2信使核糖核酸的水平。

DNA damage increases the levels of MDM2 messenger RNA in wtp53 human cells.

作者信息

Price B D, Park S J

机构信息

Joint Center for Radiation Therapy, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.

出版信息

Cancer Res. 1994 Feb 15;54(4):896-9.

PMID:8313378
Abstract

Damage to chromosomal DNA increases the levels of the transcriptional regulatory protein p53. We have investigated how the MDM2 protein, which binds to p53 and inactivates its transcriptional activity, may be controlled following DNA damage. Irradiation of human GM2149 fibroblast cells causes an increase in MDM2 mRNA levels within 1 h, and levels remain elevated for at least 8 h. The induction of MDM2 mRNA following irradiation is not blocked by inhibitors of protein synthesis and can be detected after doses of 2-5 Gy. In ataxia telangiectasia cells or cells where p53 is mutated/deleted, MDM2 mRNA levels are not increased after DNA damage. This suggests that p53 is required for transcription of the MDM2 gene following DNA damage.

摘要

染色体DNA的损伤会提高转录调节蛋白p53的水平。我们研究了与p53结合并使其转录活性失活的MDM2蛋白在DNA损伤后是如何被调控的。对人GM2149成纤维细胞进行辐射会在1小时内使MDM2 mRNA水平升高，且该水平至少8小时保持升高。辐射后MDM2 mRNA的诱导不受蛋白质合成抑制剂的阻断，在2 - 5戈瑞的剂量后即可检测到。在共济失调毛细血管扩张症细胞或p53发生突变/缺失的细胞中，DNA损伤后MDM2 mRNA水平不会升高。这表明DNA损伤后MDM2基因的转录需要p53。

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1
DNA damage increases the levels of MDM2 messenger RNA in wtp53 human cells.DNA损伤会增加野生型p53人类细胞中MDM2信使核糖核酸的水平。
Cancer Res. 1994 Feb 15;54(4):896-9.
2
Differential expression of multiple MDM2 messenger RNAs and proteins in normal and tumorigenic breast epithelial cells.多种MDM2信使核糖核酸和蛋白质在正常及致瘤性乳腺上皮细胞中的差异表达。
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The p53 mRNA-Mdm2 interaction controls Mdm2 nuclear trafficking and is required for p53 activation following DNA damage.p53mRNA-Mdm2 相互作用控制 Mdm2 的核转运，并且是 DNA 损伤后 p53 激活所必需的。
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Interactions between p53 and MDM2 in a mammalian cell cycle checkpoint pathway.p53与MDM2在哺乳动物细胞周期检查点通路中的相互作用。
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Mdm2: keeping p53 under control.Mdm2：调控p53。
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The high levels of p53 present in adenovirus early region 1-transformed human cells do not cause up-regulation of MDM2 expression.腺病毒早期区域1转化的人细胞中存在的高水平p53不会导致MDM2表达上调。
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Enhanced MDM2 Oncoprotein Expression in Soft Tissue Sarcoma: Several Possible Regulatory Mechanisms.软组织肉瘤中MDM2癌蛋白表达增强：几种可能的调控机制
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Mdm2: the ups and downs.Mdm2：兴衰起伏。
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The human oncoprotein MDM2 arrests the cell cycle: elimination of its cell-cycle-inhibitory function induces tumorigenesis.人类癌蛋白MDM2会使细胞周期停滞：消除其细胞周期抑制功能会诱发肿瘤形成。
EMBO J. 1998 May 1;17(9):2513-25. doi: 10.1093/emboj/17.9.2513.
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Effects of p53 mutants derived from lung carcinomas on the p53-responsive element (p53RE) of the MDM2 gene.源自肺癌的p53突变体对MDM2基因的p53反应元件（p53RE）的影响。
Br J Cancer. 1998;77(3):374-84. doi: 10.1038/bjc.1998.60.
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The p53 status of Chinese hamster V79 cells frequently used for studies on DNA damage and DNA repair.常用于DNA损伤与DNA修复研究的中国仓鼠V79细胞的p53状态。
Nucleic Acids Res. 1997 Mar 1;25(5):992-4. doi: 10.1093/nar/25.5.992.
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A polymorphism but no mutations in the GADD45 gene in breast cancers.
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