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表达端粒相关蛋白 Ft1 减少的小鼠表现出 p53 敏感的早老样特征。

Mice with reduced expression of the telomere-associated protein Ft1 develop p53-sensitive progeroid traits.

机构信息

Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza Università di Roma, Rome, Italy.

Dipartimento di Ricerca, Diagnostica Avanzata e Innovazione Tecnologica, Istituto Nazionale Tumori Regina Elena, Rome, Italy.

出版信息

Aging Cell. 2018 Aug;17(4):e12730. doi: 10.1111/acel.12730. Epub 2018 Apr 10.

DOI:10.1111/acel.12730
PMID:29635765
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6052474/
Abstract

Human AKTIP and mouse Ft1 are orthologous ubiquitin E2 variant proteins involved in telomere maintenance and DNA replication. AKTIP also interacts with A- and B-type lamins. These features suggest that Ft1 may be implicated in aging regulatory pathways. Here, we show that cells derived from hypomorph Ft1 mutant (Ft1 ) mice exhibit telomeric defects and that Ft1 animals develop progeroid traits, including impaired growth, skeletal and skin defects, abnormal heart tissue, and sterility. We also demonstrate a genetic interaction between Ft1 and p53. The analysis of mice carrying mutations in both Ft1 and p53 (Ft1 ; p53 and Ft1 ; p53 ) showed that reduction in p53 rescues the progeroid traits of Ft1 mutants, suggesting that they are at least in part caused by a p53-dependent DNA damage response. Conversely, Ft1 reduction alters lymphomagenesis in p53 mutant mice. These results identify Ft1 as a new player in the aging process and open the way to the analysis of its interactions with other progeria genes using the mouse model.

摘要

人类 AKTIP 和小鼠 Ft1 是参与端粒维持和 DNA 复制的同源泛素 E2 变体蛋白。AKTIP 还与 A 型和 B 型层粘连蛋白相互作用。这些特征表明 Ft1 可能参与衰老调节途径。在这里，我们表明源自功能降低的 Ft1 突变体（Ft1 ）小鼠的细胞表现出线粒体缺陷，并且 Ft1 动物表现出进行性衰老特征，包括生长受损、骨骼和皮肤缺陷、心脏组织异常和不育。我们还证明了 Ft1 和 p53 之间存在遗传相互作用。对同时携带 Ft1 和 p53 突变的小鼠（Ft1 ；p53 和 Ft1 ；p53 ）进行分析表明，p53 的减少挽救了 Ft1 突变体的进行性衰老特征，这表明它们至少部分是由 p53 依赖性 DNA 损伤反应引起的。相反，Ft1 的减少改变了 p53 突变小鼠的淋巴瘤发生。这些结果将 Ft1 确定为衰老过程中的一个新参与者，并为使用小鼠模型分析其与其他进行性衰老基因的相互作用开辟了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddd/6052474/16339f6e385c/ACEL-17-na-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddd/6052474/27dbd53d9545/ACEL-17-na-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddd/6052474/7f360550e4a5/ACEL-17-na-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddd/6052474/70f476134297/ACEL-17-na-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddd/6052474/133928c17233/ACEL-17-na-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddd/6052474/d8ab2aa303e6/ACEL-17-na-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddd/6052474/16339f6e385c/ACEL-17-na-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddd/6052474/27dbd53d9545/ACEL-17-na-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddd/6052474/7f360550e4a5/ACEL-17-na-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddd/6052474/70f476134297/ACEL-17-na-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddd/6052474/133928c17233/ACEL-17-na-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddd/6052474/d8ab2aa303e6/ACEL-17-na-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddd/6052474/16339f6e385c/ACEL-17-na-g006.jpg

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2
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