The proteasome activator PA28γ, a negative regulator of p53, is transcriptionally up-regulated by p53.

The proteasome activator PA28γ, a negative regulator of p53, is transcriptionally up-regulated by p53.
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DOI:
10.3390/ijms15022573
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发表时间:
2014-02-13
影响因子:
5.6
通讯作者:
Zhou JL
Zhou JL
中科院分区:
生物学2区
文献类型:
--
作者:
Wan ZX;Yuan DM;Zhuo YM;Yi X;Zhou J;Xu ZX;Zhou JL

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PA 28 γ(也称为REGγ、11 S γ或PSME 3)通过促进其核输出和/或降解来负调节p53活性。本研究利用RNA连接酶介导的cDNA末端快速扩增(RLM-RACE)方法,对PA 28 γ基因的转录起始位点进行了鉴定。用荧光素酶测定法进行的评估表明,序列-193至+16是基础启动子。利用生物信息学方法在PA 28 γ启动子中发现了3个p53结合位点,并通过染色质免疫沉淀和生物素化DNA亲和沉淀实验进行了验证。p53蛋白可促进PA 28 γ的转录,PA 28 γ本身可抑制p53蛋白对PA 28 γ的转录。我们的研究结果表明,PA 28 γ和p53形成负反馈回路,维持细胞内p53和PA 28 γ的平衡。
PA28γ (also called REGγ, 11Sγ or PSME3) negatively regulates p53 activity by promoting its nuclear export and/or degradation. Here, using the RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE) method, we identified the transcription start site of the PA28γ gene. Assessment with the luciferase assay demonstrated that the sequence −193 to +16 is the basal promoter. Three p53 binding sites were found within the PA28γ promoter utilizing a bioinformatics approach and were confirmed by chromatin immunoprecipitation and biotinylated DNA affinity precipitation experiments. The p53 protein promotes PA28γ transcription, and p53-stimulated transcription of PA28γ can be inhibited by PA28γ itself. Our results suggest that PA28γ and p53 form a negative feedback loop, which maintains the balance of p53 and PA28γ in cells.
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