更新于：2024-11-01

PARIS

更新于：2024-11-01

基本信息

别名

FLJ31413、PARIS、Parkin-interacting substrate

+ [2]

简介

Transcription repressor that specifically binds to the 5'-TATTTT[T/G]-3' consensus sequence on promoters and repress transcription of PGC-1-alpha (PPARGC1A), thereby playing a role in regulation of neuron death.

关联

项与 PARIS 相关的药物

Farnesol

法呢醇

靶点

PARIS

作用机制

PARIS inhibitors

在研机构

Samsung Biomedical Research Institute [+1]

原研机构

Samsung Biomedical Research Institute

在研适应症

帕金森病 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 PARIS 相关的临床结果

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100 项与 PARIS 相关的转化医学

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0 项与 PARIS 相关的专利（医药）

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项与 PARIS 相关的文献（医药）

2024-10-10·Nature

Architecture and activation mechanism of the bacterial PARIS defence system

Article

作者: Enustun, Eray ; Liang, Qishan ; Deep, Amar ; Pogliano, Joe ; Corbett, Kevin D

Bacteria and their viruses (bacteriophages or phages) are engaged in an intense evolutionary arms race^1-5. While the mechanisms of many bacterial antiphage defence systems are known¹, how these systems avoid toxicity outside infection yet activate quickly after infection is less well understood. Here we show that the bacterial phage anti-restriction-induced system (PARIS) operates as a toxin-antitoxin system, in which the antitoxin AriA sequesters and inactivates the toxin AriB until triggered by the T7 phage counterdefence protein Ocr. Using cryo-electron microscopy, we show that AriA is related to SMC-family ATPases but assembles into a distinctive homohexameric complex through two oligomerization interfaces. In uninfected cells, the AriA hexamer binds to up to three monomers of AriB, maintaining them in an inactive state. After Ocr binding, the AriA hexamer undergoes a structural rearrangement, releasing AriB and allowing it to dimerize and activate. AriB is a toprim/OLD-family nuclease, the activation of which arrests cell growth and inhibits phage propagation by globally inhibiting protein translation through specific cleavage of a lysine tRNA. Collectively, our findings reveal the intricate molecular mechanisms of a bacterial defence system triggered by a phage counterdefence protein, and highlight how an SMC-family ATPase has been adapted as a bacterial infection sensor.

2024-10-10·Nature

A virally encoded tRNA neutralizes the PARIS antiviral defence system

Article

作者: Buyukyoruk, Murat ; Wiedenheft, Blake ; Wilkinson, Royce A ; Depardieu, Florence ; Belukhina, Svetlana ; Zahl, Trevor ; Chechenina, Anna ; Rouillon, Christophe ; Tesson, Florian ; Santiago-Frangos, Andrew ; Koszul, Romain ; Saudemont, Baptiste ; Hauryliuk, Vasili ; Isaev, Artem ; Morozova, Natalia ; Thierry, Agnès ; Shyrokova, Lena ; Skutel, Mikhail ; Bernheim, Aude ; Henriques, William S ; Burman, Nathaniel ; Livenskyi, Alexei ; Kurata, Tatsuaki ; Groseille, Justine ; Bikard, David ; Graham, Ava B ; Severinov, Konstantin

Viruses compete with each other for limited cellular resources, and some deliver defence mechanisms that protect the host from competing genetic parasites¹. The phage antirestriction induced system (PARIS) is a defence system, often encoded in viral genomes, that is composed of a 55 kDa ABC ATPase (AriA) and a 35 kDa TOPRIM nuclease (AriB)². However, the mechanism by which AriA and AriB function in phage defence is unknown. Here we show that AriA and AriB assemble into a 425 kDa supramolecular immune complex. We use cryo-electron microscopy to determine the structure of this complex, thereby explaining how six molecules of AriA assemble into a propeller-shaped scaffold that coordinates three subunits of AriB. ATP-dependent detection of foreign proteins triggers the release of AriB, which assembles into a homodimeric nuclease that blocks infection by cleaving host lysine transfer RNA. Phage T5 subverts PARIS immunity through expression of a lysine transfer RNA variant that is not cleaved by PARIS, thereby restoring viral infection. Collectively, these data explain how AriA functions as an ATP-dependent sensor that detects viral proteins and activates the AriB toxin. PARIS is one of an emerging set of immune systems that form macromolecular complexes for the recognition of foreign proteins, rather than foreign nucleic acids³.

2024-06-01·Neuroscience Research

Unveiling the regulatory of miR-101-3p on ZNF746 in a Parkinson's disease cell model: Implications for therapeutic targeting

Article

作者: Peymani, Maryam ; Mostashfi, Maryam ; Nasr-Esfahani, Mohammad Hossein ; Angaji, Seyed Abdolhamid ; Mahmoudian Esfahani, Maryam ; Hashemi, Motahare-Sadat ; Vaheb Hosseinabadi, Shiva ; Zohrabi, Dina ; Ghaedi, Kamran

In this study, we explored the regulatory role of microRNA miR-101-3p on the zinc finger protein 746 (ZNF746), also known as PARIS, which is implicated in both sporadic and familial forms of Parkinson's disease. In a Parkinson's disease cell model, utilizing SH-SY5Y cells treated with 1-methyl-4-phenylpyridine (MPP+), we observed that miR-101-3p was downregulated, while ZNF746 was upregulated. To investigate the direct impact of miR-101-3p on ZNF746, our team conducted overexpression experiments, successfully reversing ZNF746's expression at both the mRNA and protein levels, as confirmed through quantitative PCR and western blotting. We also performed luciferase assays, providing compelling evidence that ZNF746 is a direct target of miR-101-3p. Additionally, we noted that miR-101-3p overexpression resulted in increased expression of PGC1α, a gene targeted by ZNF746. Functionally, we assessed the implications of miR-101-3p overexpression through MTS assays and flow cytometry, revealing significant promotion of cell viability, inhibition of ROS production, and reduced apoptosis in the Parkinson's disease cell model. In conclusion, this study highlights the role of miR-101-3p in regulating ZNF746 expression and suggests its potential as a therapeutic target for Parkinson's disease. These findings provide valuable molecular insights that could pave the way for innovative treatment strategies in combating this debilitating neurodegenerative disorder.