@article{1caea396f626450fb04bd44aeaa1b5fb,
title = "Phosphorylation of IRE1 at S729 regulates RIDD in B cells and antibody production after immunization",
abstract = "To relieve endoplasmic reticulum (ER) stress, IRE1 splices XBP1 messenger RNA (mRNA) or engages regulated IRE1- dependent decay (RIDD) of other mRNAs. Upon XBP1 deficiency, IRE1 switches to perform RIDD. We examined IRE1 in XBP1-deficient B cells and discovered that IRE1 undergoes phosphorylation at S729. We generated an anti-phospho-S729 antibody to investigate such phosphorylation. Compared with pharmacological ER stress inducers or Toll-like receptor ligands, the bacterial subtilase cytotoxin has an unusual capability in causing rapid and strong phosphorylation at S729 and triggering B cells to express spliced XBP1. To assess the function of S729 in IRE1, we generated S729A knock-in mice and found S729 is critically important for lipopolysaccharide-stimulated plasmablasts to respond to additional ER stress and for antibody production in response to immunization. We further crossed mice carrying an S729A mutation or ΔIRE1 (missing the kinase domain) with B cell-specific XBP1-deficient mice to trigger RIDD and discovered a critical role for S729 in regulating RIDD in B cells.",
author = "{Anthony Tang}, {Chih Hang} and Shiun Chang and Paton, {Adrienne W.} and Paton, {James C.} and Gabrilovich, {Dmitry I.} and Ploegh, {Hidde L.} and {Del Valle}, {Juan R.} and {Andrew Hu}, {Chih Chi}",
note = "Funding Information: to detect the expression of mouse μS, 5 㰀-CAACCTGTACAATGT Fig. S4 documents normal B and T cell percentages in the spleens CTCCCT-3 㰀 and 5 㰀-AATAGACAACATCTCACTCTG-3 㰀; mouse UBC, and lymph nodes of unimmunized S729A mice and shows that 5 㰀-CACGCGTATATCTTCCCAGACT-3 㰀 and 5 㰀-ACGTACGGGATGCCA after immunization, the percentages of CD19+ B cells decrease GTAATCTA-3 㰀; mouse XBP1s, 5 㰀-CGATTCGGGAAGATGTTCTGG-3 ? in the lymph nodes, whereas the percentages of CD4+ and CD8+ and 5 ?-CTAG TCCGAATCAGGTGCAG-3 ?; mouse Hspa5, 5 ?-TGTT cells increase in the spleens and lymph nodes of S729A mice. CTTCTCAGCATCAAGCAAGG-3 㰀an d 5 㰀-CCAACACTTTCTGGA Fig. S5 shows that LPS-stimulated B cells from S729A mice fail to CAGGCTT-3 㰀; mouse Pdia4, 5 㰀-CGTGCGTTTCAGGGAGATGG-3 ? respond to Tg or SubAB by enhancing the expression of XBP1s. and 5 㰀-GGAGGACTTTCAGGAACTTGGC-3 㰀; mouse Itgb2, 5 㰀-CTT TCCGAGAGCAACATCCAGC-3 㰀 and 5 㰀-GGCTTGGAGTCGTCAGA CAGT-3 㰀; mouse Ergic3, 5 㰀-CGATATGAAACGACTAGACAAGGA-Acknowledgments 3 㰀 and 5 㰀-TACCGCACTTTCCCAAGCTC-3 㰀; mouse Bloc1S1, 5 㰀-GAGWe thank Joseph A. Zundell and Yi-Ju Chen for the technical GAGAGAAGCTATCGCTGCA-3 㰀 and 5 㰀-GCATCGCTGTAGAGTCTT assistance in mouse genotyping and immunoblots, Dr. Deyu CACC-3 ?; mouse Tapbp1, 5 ?-ATCTCCCCAGGAACTCAAA-3 ? and Fang for providing us with IRE1f/f mice, and Dr. Dario C. Altieri 5 㰀-GAAGAGAAGGCTGTTGTTCTGG-3 㰀; mouse Hgsnat, 5 㰀-CTCCGT for reading the manuscript. CTTTCTCCATTTTG-3 㰀 and 5 㰀-ACTGACCACGTGGAAAGTCA-3 㰀; This study was partially supported by grants from the National mouse Scara3, 5 㰀-TGACTGGATACTGACCCTGA-3 㰀 and 5 㰀-GGTCGC Institutes of Health/National Cancer Institute (R01CA163910, TTACCAGCTTCTTC-3 㰀; mouse Col6a1, 5 㰀-TCGACACATGAAGC R21CA199553, R01CA190860, and R01CA100062). AGACC-3 ? and 5 ?-ATGTGGAGAAAGCTCTGGA-3 ?; and mouse The authors declare no competing financial interests. Pdgfrb, 5 㰀-AACCCCTTACAGCTGTCCT-3 㰀 and 5 㰀-TCACACGT Author contributions: C.-H.A. Tang, S. Chang, and C.-C.A. CAGCATCTTCC-3 㰀. Hu designed the research. C.-H.A. Tang, S. Chang, A.W. Paton, J.C. Paton, D.I. Gabrilovich, H.L. Ploegh, J.R. Del Valle, and C.-C.A. Publisher Copyright: {\textcopyright} 2018 Tang et al.",
year = "2018",
month = may,
day = "1",
doi = "10.1083/jcb.201709137",
language = "English (US)",
volume = "217",
pages = "1739--1755",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "5",
}