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Phosphoregulation of Ire1 RNase splicing activity

Prischi, Filippo and Nowak, Piotr R and Carrara, Marta and Ali, Maruf MU (2014) 'Phosphoregulation of Ire1 RNase splicing activity.' Nature Communications, 5 (1). 3554-. ISSN 2041-1723

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Abstract

<jats:title>Abstract</jats:title> <jats:p>Ire1 is activated in response to accumulation of misfolded proteins within the endoplasmic reticulum as part of the unfolded protein response (UPR). It is a unique enzyme, possessing both kinase and RNase activity that is required for specific splicing of Xbp1 mRNA leading to UPR activation. How phosphorylation impacts on the Ire1 splicing activity is unclear. In this study, we isolate distinct phosphorylated species of Ire1 and assess their effects on RNase splicing both <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic>. We find that phosphorylation within the kinase activation loop significantly increases RNase splicing <jats:italic>in vitro.</jats:italic> Correspondingly, mutants of Ire1 that cannot be phosphorylated on the activation loop show decreased specific Xbp1 and promiscuous RNase splicing activity relative to wild-type Ire1 in cells. These data couple the kinase phosphorylation reaction to the activation state of the RNase, suggesting that phosphorylation of the activation loop is an important step in Ire1-mediated UPR activation.</jats:p>

Item Type: Article
Uncontrolled Keywords: Cell Line, Tumor; Humans; Endoribonucleases; DNA-Binding Proteins; Transcription Factors; Blotting, Western; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Reverse Transcriptase Polymerase Chain Reaction; Phosphorylation; Sf9 Cells; Regulatory Factor X Transcription Factors; X-Box Binding Protein 1; Protein Serine-Threonine Kinases
Subjects: Q Science > Q Science (General)
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 18 Dec 2015 17:03
Last Modified: 18 Aug 2022 11:31
URI: http://repository.essex.ac.uk/id/eprint/14832

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