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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Auteurs principaux:	Evelyn Chukwurah, Rekha C. Patel
Format:	article
Langue:	EN
Publié:	Nature Portfolio 2018
Sujets:	Medicine R Science Q
Accès en ligne:	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
_version_	1718387889873616896

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

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