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剃毛婴儿和约克夏梗介导 Hippo 信号通路以保护成体干细胞免于细胞凋亡。

Shavenbaby and Yorkie mediate Hippo signaling to protect adult stem cells from apoptosis.

机构信息

Centre de Biologie du Développement (CBD), Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, Bat 4R3, 118 route de Narbonne, F-31062, Toulouse, France.

Faculty of Sciences III, Lebanese University, Tripoli, 1300, Lebanon.

出版信息

Nat Commun. 2018 Nov 30;9(1):5123. doi: 10.1038/s41467-018-07569-0.

DOI:10.1038/s41467-018-07569-0
PMID:30504772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6269459/
Abstract

To compensate for accumulating damages and cell death, adult homeostasis (e.g., body fluids and secretion) requires organ regeneration, operated by long-lived stem cells. How stem cells can survive throughout the animal life remains poorly understood. Here we show that the transcription factor Shavenbaby (Svb, OvoL in vertebrates) is expressed in renal/nephric stem cells (RNSCs) of Drosophila and required for their maintenance during adulthood. As recently shown in embryos, Svb function in adult RNSCs further needs a post-translational processing mediated by the Polished rice (Pri) smORF peptides and impairing Svb function leads to RNSC apoptosis. We show that Svb interacts both genetically and physically with Yorkie (YAP/TAZ in vertebrates), a nuclear effector of the Hippo pathway, to activate the expression of the inhibitor of apoptosis DIAP1. These data therefore identify Svb as a nuclear effector in the Hippo pathway, critical for the survival of adult somatic stem cells.

摘要

为了补偿积累的损伤和细胞死亡,成体稳态(例如,体液和分泌物)需要由长寿干细胞进行器官再生。干细胞如何在整个动物生命过程中存活仍然知之甚少。在这里,我们表明转录因子 Shavenbaby(Svb,脊椎动物中的 OvoL)在果蝇的肾脏/肾单位干细胞(RNSC)中表达,并在成年期维持其存活。正如最近在胚胎中显示的那样,Svb 在成年 RNSC 中的功能还需要由 Polished rice(Pri)smORF 肽介导的翻译后加工,并且破坏 Svb 功能会导致 RNSC 凋亡。我们表明,Svb 与 Yorkie(脊椎动物中的 YAP/TAZ)在遗传和物理上相互作用,Yorkie 是 Hippo 途径的核效应物,以激活凋亡抑制剂 DIAP1 的表达。因此,这些数据确定 Svb 作为 Hippo 途径中的核效应物,对于成年体干细胞的存活至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7730/6269459/387358a9367a/41467_2018_7569_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7730/6269459/196b3248e8f3/41467_2018_7569_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7730/6269459/ece38e1450a6/41467_2018_7569_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7730/6269459/fc110c80aea8/41467_2018_7569_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7730/6269459/ff5a7bd77b58/41467_2018_7569_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7730/6269459/dadc187de3f0/41467_2018_7569_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7730/6269459/53729d752693/41467_2018_7569_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7730/6269459/ba7e340dd6b0/41467_2018_7569_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7730/6269459/387358a9367a/41467_2018_7569_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7730/6269459/196b3248e8f3/41467_2018_7569_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7730/6269459/ece38e1450a6/41467_2018_7569_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7730/6269459/fc110c80aea8/41467_2018_7569_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7730/6269459/ff5a7bd77b58/41467_2018_7569_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7730/6269459/dadc187de3f0/41467_2018_7569_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7730/6269459/53729d752693/41467_2018_7569_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7730/6269459/ba7e340dd6b0/41467_2018_7569_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7730/6269459/387358a9367a/41467_2018_7569_Fig8_HTML.jpg

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