Abstract
P58IPK has been implicated in eukaryotic ER stress responses and viral pathogenesis, however, its biological functions and molecular mechanism in plants are unclear. Prolonged ER stress produced by tunicamycin (TM) increased P58IPK mRNA and protein levels in Arabidopsis. Although the growth of 2 × 35S:P58IPK-myc plants was less severely inhibited than that of Col-0 plants, TM inhibited the growth of p58ipk-2 mutants more severely than that of Col-0 plants. Under prolonged ER stress conditions, the unfolded protein response (UPR)-related genes were expressed at a higher level in the p58ipk-2 mutants than in Col-0 plants. Protein synthesis inhibition by TM in 2 × 35S:P58IPK-myc plants was lower than in Col-0 plants under prolonged ER stress conditions, however, not significantly different in p58ipk-2 mutants. The GST-P58IPK protein exhibited both chaperone and RNA-binding activities in a dose-dependent manner. P58IPK has been shown to interact with ribosomes, allowing for enhanced protein production on the ER membrane. Following ER stress, 2 × 35S:P58IPK-myc plants recovered better than Col-0, but p58ipk-2 mutants recovered less than Col-0. These findings reveal that P58IPK can promote protein translation in association with ribosomes and contribute to stress recovery in Arabidopsis when induced during the last phase of ER stress.
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Alonso JM, Stepanova AN, Leisse TJ, Kim CJ, Chen H, Shinn P, Stevenson DK, Zimmerman J, Barajas P, Cheuk R, Gadrinab C, Heller C, Jeske A, Koesema E, Meyers CC, Parker H, Prednis L, Ansari Y, Choy N, Deen H, Geralt M, Hazari N, Hom E, Karnes M, Mulholland C, Ndubaku R, Schmidt I, Guzman P, Aguilar-Henonin L, Schmid M, Weigel D, Carter DE, Marchand T, Risseeuw E, Brogden D, Zeko A, Crosby WL, Berry CC, Ecker JR (2003) Genome-wide insertional mutagenesis of Arabidopsis thaliana. Science 301:653–657
Anelli T, Sitia R (2008) Protein quality control in the early secretory pathway. EMBO J 27:315–327
Azzam ME, Algranati ID (1973) Mechanism of puromycin action: fate of ribosomes after release of nascent protein chains from polysomes. Proc Natl Acad Sci USA 70:3866–3869
Balchin D, Hayer-Hartl M, Hartl FU (2016) In vivo aspects of protein folding and quality control. Science 353:aac4354
Bilgin DD, Liu Y, Schiff M, Dinesh-Kumar SP (2003) P58(IPK), a plant ortholog of double-stranded RNA-dependent protein kinase PKR inhibitor, functions in viral pathogenesis. Dev Cell 4:651–661
Boyce M, Bryant KF, Jousse C, Long K, Harding HP, Scheuner D, Kaufman RJ, Ma D, Coen DM, Ron D, Yuan J (2005) A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress. Science 307:935–939
Carpenter CD, Kreps JA, Simon AE (1994) Genes encoding glycine-rich Arabidopsis thaliana proteins with RNA-binding motifs are influenced by cold treatment and an endogenous circadian rhythm. Plant Physiol 104:1015–1025
Chen Q, Zhong Y, Wu Y, Liu L, Wang P, Liu R, Cui F, Li Q, Yang X, Fang S, Xie Q (2016) HRD1-mediated ERAD tuning of ER-bound E2 is conserved between plants and mammals. Nat Plants 2:16094
Chen Q, Liu R, Wang Q, Xie Q (2017) ERAD tuning of the HRD1 complex component AtOS9 is modulated by an ER-bound E2, UBC32. Mol Plant 10:891–894
D’andrea LD, Regan L (2003) TPR proteins: the versatile helix. Trends Biochem Sci 28:655–662
Dempsey DMA, Pathirana MS, Wobbe KK, Klessig DF (1997) Identification of an Arabidopsis locus required for resistance to turnip crinkle virus. Plant J 11:301–311
Ellgaard L, Helenius A (2003) Quality control in the endoplasmic reticulum. Nat Rev Mol Cell Biol 4:181–191
Gale M Jr, Tan SL, Wambach M, Katze MG (1996) Interaction of the interferon-induced PKR protein kinase with inhibitory proteins P58IPK and vaccinia virus K3L is mediated by unique domains: implications for kinase regulation. Mol Cell Biol 16:4172–4181
Genevaux P, Schwager F, Georgopoulos C, Kelley WL (2002) Scanning mutagenesis identifies amino acid residues essential for the in vivo activity of the Escherichia coli DnaJ (Hsp40) J-domain. Genetics 162:1045–1053
Goebl M, Yanagida M (1991) The TPR snap helix: a novel protein repeat motif from mitosis to transcription. Trends Biochem Sci 16:173–177
Gomord V, Denmat LA, Fitchette-Laine AC, Satiat-Jeunemaitre B, Hawes C, Faye L (1997) The C-terminal HDEL sequence is sufficient for retention of secretory proteins in the endoplasmic reticulum (ER) but promotes vacuolar targeting of proteins that escape the ER. Plant J 11:313–325
Goodman AG, Smith JA, Balachandran S, Perwitasari O, Proll SC, Thomas MJ, Korth MJ, Barber GN, Schiff LA, Katze MG (2007) The cellular protein P58IPK regulates influenza virus mRNA translation and replication through a PKR-mediated mechanism. J Virol 81:2221–2230
Guan BJ, Van Hoef V, Jobava R, Elroy-Stein O, Valasek LS, Cargnello M, Gao XH, Krokowski D, Merrick WC, Kimball SR, Komar AA, Koromilas AE, Wynshaw-Boris A, Topisirovic I, Larsson O, Hatzoglou M (2017) A unique ISR program determines cellular responses to chronic stress. Mol Cell 68(885–900):e886
Harding HP, Zhang Y, Ron D (1999) Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 397:271–274
Harding HP, Calfon M, Urano F, Novoa I, Ron D (2002) Transcriptional and translational control in the mammalian unfolded protein response. Annu Rev Cell Dev Biol 18:575–599
Hofmann K (1993) TM base-a database of membrane spanning proteins segments. Biol Chem Hoppe-Seyler 374:166
Holcik M, Sonenberg N (2005) Translational control in stress and apoptosis. Nat Rev Mol Cell Biol 6:318–327
Hou Z, Pang X, Hedtke B, Grimm B (2021) In vivo functional analysis of the structural domains of fluorescent (FLU). Plant J 107:360–376
Jackson RJ, Hellen CU, Pestova TV (2010) The mechanism of eukaryotic translation initiation and principles of its regulation. Nat Rev Mol Cell Biol 11:113–127
Kamauchi S, Nakatani H, Nakano C, Urade R (2005) Gene expression in response to endoplasmic reticulum stress in Arabidopsis thaliana. FEBS J 272:3461–3476
Kelley WL (1998) The J-domain family and the recruitment of chaperone power. Trends Biochem Sci 23:222–227
Khoury GA, Baliban RC, Floudas CA (2011) Proteome-wide post-translational modification statistics: frequency analysis and curation of the swiss-prot database. Sci Rep. https://doi.org/10.1038/srep00090
Ko DK, Brandizzi F (2022) Advanced genomics identifies growth effectors for proteotoxic ER stress recovery in Arabidopsis thaliana. Commun Biol 5:16
Kolli R, Soll J, Carrie C (2019) OXA2b is crucial for proper membrane insertion of COX2 during biogenesis of complex IV in plant mitochondria. Plant Physiol 179:601–615
Kozutsumi Y, Segal M, Normington K, Gething MJ, Sambrook J (1988) The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins. Nature 332:462–464
Kriechbaumer V, Von Loffelholz O, Abell BM (2012) Chaperone receptors: guiding proteins to intracellular compartments. Protoplasma 249:21–30
Lamb JR, Tugendreich S, Hieter P (1995) Tetratrico peptide repeat interactions: to TPR or not to TPR? Trends Biochem Sci 20:257–259
Lecompte O, Ripp R, Thierry JC, Moras D, Poch O (2002) Comparative analysis of ribosomal proteins in complete genomes: an example of reductive evolution at the domain scale. Nucleic Acids Res 30:5382–5390
Lee TG, Tang N, Thompson S, Miller J, Katze MG (1994) The 58,000-dalton cellular inhibitor of the interferon-induced double-stranded RNA-activated protein kinase (PKR) is a member of the tetratricopeptide repeat family of proteins. Mol Cell Biol 14:2331–2342
Lee JR, Lee SS, Jang HH, Lee YM, Park JH, Park SC, Moon JC, Park SK, Kim SY, Lee SY, Chae HB, Jung YJ, Kim WY, Shin MR, Cheong GW, Kim MG, Kang KR, Lee KO, Yun DJ (2009) Heat-shock dependent oligomeric status alters the function of a plant-specific thioredoxin-like protein, AtTDX. Proc Natl Acad Sci USA 106:5978–5983
Lee K, Thwin AC, Nadel CM, Tse E, Gates SN, Gestwicki JE, Southworth DR (2021) The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state. Mol Cell 81:3496–3508
Li J, Liu J, Wang G, Cha JY, Li G, Chen S, Li Z, Guo J, Zhang C, Yang Y, Kim WY, Yun DJ, Schumaker KS, Chen Z, Guo Y (2015) A chaperone function of no catalase activity1 is required to maintain catalase activity and for multiple stress responses in Arabidopsis. Plant Cell 27:908–925
Liu Z, Lv Y, Zhao N, Guan G, Wang J (2015) Protein kinase R-like ER kinase and its role in endoplasmic reticulum stress-decided cell fate. Cell Death Dis 6:e1822
Mann M, Jensen ON (2003) Proteomic analysis of post-translational modifications. Nat Biotechnol 21:255–261
Melville MW, Tan SL, Wambach M, Song J, Morimoto RI, Katze MG (1999) The cellular inhibitor of the PKR protein kinase, P58(IPK), is an influenza virus-activated co-chaperone that modulates heat shock protein 70 activity. J Biol Chem 274:3797–3803
Mishiba K, Nagashima Y, Suzuki E, Hayashi N, Ogata Y, Shimada Y, Koizumi N (2013) Defects in IRE1 enhance cell death and fail to degrade mRNAs encoding secretory pathway proteins in the Arabidopsis unfolded protein response. Proc Natl Acad Sci USA 110:5713–5718
Moon JY, Lee JH, Oh CS, Kang HG, Park JM (2016) Endoplasmic reticulum stress responses function in the HRT-mediated hypersensitive response in Nicotiana benthamiana. Mol Plant Pathol 17:1382–1397
Mori K (2000) Tripartite management of unfolded proteins in the endoplasmic reticulum. Cell 101:451–454
Moriguchi K, Sugita M, Sugiura M (1997) Structure and subcellular localization of a small RNA-binding protein from tobacco. Plant J 12:215–221
Noel LD, Cagna G, Stuttmann J, Wirthmuller L, Betsuyaku S, Witte CP, Bhat R, Pochon N, Colby T, Parker JE (2007) Interaction between SGT1 and cytosolic/nuclear HSC70 chaperones regulates Arabidopsis immune responses. Plant Cell 19:4061–4076
Nomata T, Kabeya Y, Sato N (2004) Cloning and characterization of glycine-rich RNA-binding protein cDNAs in the moss Physcomitrella patens. Plant Cell Physiol 45:48–56
Ohoka N, Yoshii S, Hattori T, Onozaki K, Hayashi H (2005) TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. EMBO J 24:1243–1255
Oyadomari S, Yun C, Fisher EA, Kreglinger N, Kreibich G, Oyadomari M, Harding HP, Goodman AG, Harant H, Garrison JL, Taunton J, Katze MG, Ron D (2006) Cotranslocational degradation protects the stressed endoplasmic reticulum from protein overload. Cell 126:727–739
Prostko CR, Brostrom MA, Brostrom CO (1993) Reversible phosphorylation of eukaryotic initiation factor 2 alpha in response to endoplasmic reticular signaling. Mol Cell Biochem 127–128:255–265
Qiu XB, Shao YM, Miao S, Wang L (2006) The diversity of the DnaJ/Hsp40 family, the crucial partners for Hsp70 chaperones. Cell Mol Life Sci 63:2560–2570
Qu F, Ren T, Morris TJ (2003) The coat protein of turnip crinkle virus suppresses posttranscriptional gene silencing at an early initiation step. J Virol 77:511
Ron D (2002) Translational control in the endoplasmic reticulum stress response. J Clin Invest 110:1383–1388
Ron D, Walter P (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8:519–529
Roobol A, Roobol J, Bastide A, Knight JR, Willis AE, Smales CM (2015) p58IPK is an inhibitor of the eIF2alpha kinase GCN2 and its localization and expression underpin protein synthesis and ER processing capacity. Biochem J 465:213–225
Rutkowski DT, Kang SW, Goodman AG, Garrison JL, Taunton J, Katze MG, Kaufman RJ, Hegde RS (2007) The role of p58IPK in protecting the stressed endoplasmic reticulum. Mol Biol Cell 18:3681–3691
Saint-Jore-Dupas C, Nebenfuhr A, Boulaflous A, Follet-Gueye ML, Plasson C, Hawes C, Driouich A, Faye L, Gomord V (2006) Plant N-glycan processing enzymes employ different targeting mechanisms for their spatial arrangement along the secretory pathway. Plant Cell 18:3182–3200
Scheuner D, Song B, Mcewen E, Liu C, Laybutt R, Gillespie P, Saunders T, Bonner-Weir S, Kaufman RJ (2001) Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol Cell 7:1165–1176
Shinozuka H, Hisano H, Yoneyama S, Shimamoto Y, Jones ES, Forster JW, Yamada T, Kanazawa A (2006) Gene expression and genetic mapping analyses of a perennial ryegrass glycine-rich RNA-binding protein gene suggest a role in cold adaptation. Mol Genet Genom 275:399–408
Sikorski RS, Boguski MS, Goebl M, Hieter P (1990) A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis. Cell 60:307–317
Spriggs KA, Bushell M, Willis AE (2010) Translational regulation of gene expression during conditions of cell stress. Mol Cell 40:228–237
Srivastava R, Deng Y, Shah S, Rao AG, Howell SH (2013) BINDING PROTEIN is a master regulator of the endoplasmic reticulum stress sensor/transducer bZIP28 in Arabidopsis. Plant Cell 25:1416–1429
Srivastava R, Li Z, Russo G, Tang J, Bi R, Muppirala U, Chudalayandi S, Severin A, He M, Vaitkevicius SI, Lawrence-Dill CJ, Liu P, Stapleton AE, Bassham DC, Brandizzi F, Howell SH (2018) Response to persistent ER stress in plants: a multiphasic process that transitions cells from prosurvival activities to cell death. Plant Cell 30:1220–1242
Strasser R (2018) Protein quality control in the endoplasmic reticulum of plants. Annu Rev Plant Biol 69:147–172
Suh WC, Burkholder WF, Lu CZ, Zhao X, Gottesman ME, Gross CA (1998) Interaction of the Hsp70 molecular chaperone, DnaK, with its cochaperone DnaJ. Proc Natl Acad Sci USA 95:15223–15228
Svard M, Biterova EI, Bourhis JM, Guy JE (2011) The crystal structure of the human co-chaperone P58(IPK). PLoS ONE 6:e22337
Tan SL, Gale MJ Jr, Katze MG (1998) Double-stranded RNA-independent dimerization of interferon-induced protein kinase PKR and inhibition of dimerization by the cellular P58IPK inhibitor. Mol Cell Biol 18:2431–2443
Tang NM, Ho CY, Katze MG (1996) The 58-kDa cellular inhibitor of the double stranded RNA-dependent protein kinase requires the tetratricopeptide repeat 6 and DnaJ motifs to stimulate protein synthesis in vivo. J Biol Chem 271:28660–28666
Tsaytler P, Harding HP, Ron D, Bertolotti A (2011) Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis. Science 332:91–94
Tusnady GE, Simon I (2001) The HMMTOP transmembrane topology prediction server. Bioinformatics 17:849–850
Van Hoewyk D (2016) Use of the non-radioactive SUnSET method to detect decreased protein synthesis in proteasome inhibited Arabidopsis roots. Plant Method 12:20
Van Huizen R, Martindale JL, Gorospe M, Holbrook NJ (2003) P58IPK, a novel endoplasmic reticulum stress-inducible protein and potential negative regulator of eIF2alpha signaling. J Biol Chem 278:15558–15564
Watanabe N, Lam E (2008) BAX inhibitor-1 modulates endoplasmic reticulum stress-mediated programmed cell death in Arabidopsis. J Biol Chem 283:3200–3210
Wu G, Otegui MS, Spalding EP (2010) The ER-localized TWD1 immunophilin is necessary for localization of multidrug resistance-like proteins required for polar auxin transport in Arabidopsis roots. Plant Cell 22:3295–3304
Yamaguchi H, Wang HG (2004) CHOP is involved in endoplasmic reticulum stress-induced apoptosis by enhancing DR5 expression in human carcinoma cells. J Biol Chem 279:45495–45502
Yamamoto M, Maruyama D, Endo T, Nishikawa S (2008) Arabidopsis thaliana has a set of J proteins in the endoplasmic reticulum that are conserved from yeast to animals and plants. Plant Cell Physiol 49:1547–1562
Yan W, Frank CL, Korth MJ, Sopher BL, Novoa I, Ron D, Katze MG (2002) Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK. Proc Natl Acad Sci USA 99:15920–15925
Yao Y, Ling Q, Wang H, Huang H (2008) Ribosomal proteins promote leaf adaxial identity. Development 135:1325–1334
Yoo JY, Ko KS, Seo HK, Park S, Fanata WI, Harmoko R, Ramasamy NK, Thulasinathan T, Mengiste T, Lim JM, Lee SY, Lee KO (2015) Limited addition of the 6-arm beta1,2-linked N-Acetylglucosamine (GlcNAc) Residue Facilitates the Formation of the Largest N-Glycan in Plants. J Biol Chem 290:16560–16572
Acknowledgements
This work was supported by the Cooperative Research Program for Agriculture Science and Technology Development (Project No. PJ016236) and by the National Research Foundation of Korea (NRF, 2021R1A2C1013516, 2019R1I1A1A01058736, 2022R1I1A1A01071947, and 2020R1A6A1A03044344) Grants funded by the Korean government (Rural Development Administration, the Ministry of Science and ICT, and Ministry of Education). B.N. Vu, Y.E. Lee, H.N. Choi and Y.N. Lee were supported by the BK4 program funded by the Ministry of Education of Korea.
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KO Lee planned, designed and organized the research and wrote the research paper. KSK, JYY, KHK, BYH, BNV, YEL, HNC, YNL, JY, JYP, WSC and JCH performed and analyzed the experiments shown in Figs. 1–8, Supporting Information Figs. 1–4 and 6, 7 and Supporting Information Tables 1, 2. KSK and JYY contributed most extensively to the work presented in this paper. MSJ and HSJ carried out and evaluated the experiments shown in Fig. 5 and in Supporting Information Fig. 5. SKJ, JMP carried out and reviewed the studies shown in Supporting Information Fig. 8. WSC, JCH, HSJ and JMP provided assistance in the study and interpretation of the data. All authors reviewed the results and approved the final version of the manuscript.
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Ko, K.S., Yoo, J.Y., Kim, K.H. et al. P58IPK facilitates plant recovery from ER stress by enhancing protein synthesis. Plant Biotechnol Rep 16, 665–681 (2022). https://doi.org/10.1007/s11816-022-00797-3
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DOI: https://doi.org/10.1007/s11816-022-00797-3