Stress-induced TRBP phosphorylation enhances its interaction with PKR to regulate cellular survival

Abstract Transactivation response element RNA-binding protein (TRBP or TARBP2) initially identified to play an important role in human immunodeficiency virus (HIV) replication also has emerged as a regulator of microRNA biogenesis. In addition, TRBP functions in signaling pathways by negatively regu...

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Autores principales: Evelyn Chukwurah, Rekha C. Patel
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/955b2a9492bb4a43a844fc7d5b2137a1
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spelling oai:doaj.org-article:955b2a9492bb4a43a844fc7d5b2137a12021-12-02T15:09:07ZStress-induced TRBP phosphorylation enhances its interaction with PKR to regulate cellular survival10.1038/s41598-018-19360-82045-2322https://doaj.org/article/955b2a9492bb4a43a844fc7d5b2137a12018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-19360-8https://doaj.org/toc/2045-2322Abstract Transactivation response element RNA-binding protein (TRBP or TARBP2) initially identified to play an important role in human immunodeficiency virus (HIV) replication also has emerged as a regulator of microRNA biogenesis. In addition, TRBP functions in signaling pathways by negatively regulating the interferon-induced double-stranded RNA (dsRNA)-activated protein kinase (PKR) during viral infections and cell stress. During cellular stress, PKR is activated and phosphorylates the α subunit of the eukaryotic translation factor eIF2, leading to the cessation of general protein synthesis. TRBP inhibits PKR activity by direct interaction as well as by binding to PKR’s two known activators, dsRNA and PACT, thus preventing their interaction with PKR. In this study, we demonstrate for the first time that TRBP is phosphorylated in response to oxidative stress and upon phosphorylation, inhibits PKR more efficiently promoting cell survival. These results establish that PKR regulation through stress-induced TRBP phosphorylation is an important mechanism ensuring cellular recovery and preventing apoptosis due to sustained PKR activation.Evelyn ChukwurahRekha C. PatelNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Evelyn Chukwurah
Rekha C. Patel
Stress-induced TRBP phosphorylation enhances its interaction with PKR to regulate cellular survival
description Abstract Transactivation response element RNA-binding protein (TRBP or TARBP2) initially identified to play an important role in human immunodeficiency virus (HIV) replication also has emerged as a regulator of microRNA biogenesis. In addition, TRBP functions in signaling pathways by negatively regulating the interferon-induced double-stranded RNA (dsRNA)-activated protein kinase (PKR) during viral infections and cell stress. During cellular stress, PKR is activated and phosphorylates the α subunit of the eukaryotic translation factor eIF2, leading to the cessation of general protein synthesis. TRBP inhibits PKR activity by direct interaction as well as by binding to PKR’s two known activators, dsRNA and PACT, thus preventing their interaction with PKR. In this study, we demonstrate for the first time that TRBP is phosphorylated in response to oxidative stress and upon phosphorylation, inhibits PKR more efficiently promoting cell survival. These results establish that PKR regulation through stress-induced TRBP phosphorylation is an important mechanism ensuring cellular recovery and preventing apoptosis due to sustained PKR activation.
format article
author Evelyn Chukwurah
Rekha C. Patel
author_facet Evelyn Chukwurah
Rekha C. Patel
author_sort Evelyn Chukwurah
title Stress-induced TRBP phosphorylation enhances its interaction with PKR to regulate cellular survival
title_short Stress-induced TRBP phosphorylation enhances its interaction with PKR to regulate cellular survival
title_full Stress-induced TRBP phosphorylation enhances its interaction with PKR to regulate cellular survival
title_fullStr Stress-induced TRBP phosphorylation enhances its interaction with PKR to regulate cellular survival
title_full_unstemmed Stress-induced TRBP phosphorylation enhances its interaction with PKR to regulate cellular survival
title_sort stress-induced trbp phosphorylation enhances its interaction with pkr to regulate cellular survival
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/955b2a9492bb4a43a844fc7d5b2137a1
work_keys_str_mv AT evelynchukwurah stressinducedtrbpphosphorylationenhancesitsinteractionwithpkrtoregulatecellularsurvival
AT rekhacpatel stressinducedtrbpphosphorylationenhancesitsinteractionwithpkrtoregulatecellularsurvival
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