REVIEW ARTICLE
Cellular response to unfolded proteins in the endoplasmic
reticulum of plants
Reiko Urade
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Japan
Introduction
The unfolded protein response (UPR) is a fundamental
system common to unicellular organisms, plants, ani-
mals, and humans, and is conserved in all eukaryotic
cells. However, there are differences in the molecular
mechanisms underlying the UPR between organisms.
In yeast, the UPR increases the folding and degrada-
tion capacities of unfolded proteins by inducing the
expression of genes related to those capacities [1]. Inos-
itol-requiring enzyme-1 (IRE1), an endoplasmic reticu-
lum (ER)-transmembrane protein that is activated by
ER stress, splices basic leucine zipper (bZIP) transcrip-
tion factor HAC1 mRNA in a nonconventional man-
ner [2,3]. HAC1 is translated from the spliced mRNA
[4–6] and subsequently activates the transcription of a
group of genes possessing UPR cis-activating regula-
tory elements in their promoter regions [7–9]. This
pathway was the first example of a protein signal that
is transduced from the ER to the nucleus, and this
finding opened the door to investigation of the details
of UPR signaling events.
In comparison with that of yeast, the UPR of mam-
malian cells is a much more complicated event, in
which general attenuation of translation, apoptosis,
and folding or degrading of unfolded proteins occurs
[10–12]. The mammalian UPR is triggered by at least

considerable attention. This review will summarize recent advances in the
plant UPR and highlight the remaining questions that have yet to be
addressed.
Abbreviations
ATF, activating transcription factor; BiP, binding protein; bZIP, basic leucine zipper; eIF2a, initiation factor-2a; ER, endoplasmic reticulum;
ERAD, ER-associated degradation; ERSE, ER stress response element; fl-2, floury-2; GFP, green fluorescent protein; GLS, Golgi body
localization sequence; GPT, UDP-N-acetylglucosamine–dolichol phosphate N-acetylglucosamine-1-phosphate transferase; IRE1, inositol-
requiring enzyme-1; PCD, programmed cell death; PDI, protein disulfide isomerase; PERK, interferon-induced dsRNA-activated protein
kinase-related protein; S1P, site-1 protease; S2P, site-2 protease; UGGT, UDP-glucose–glycoprotein glucosyltransferase; UPR, unfolded
protein response; UPS, ubiquitin-proteasome system; XBP-1, X-box binding protein 1.
1152 FEBS Journal 274 (2007) 1152–1171 ª 2007 The Author Journal compilation ª 2007 FEBS
ortholog of yeast IRE1 [13,14], activating transcription
factor (ATF) 6 [15], and interferon-induced dsRNA-
activated protein kinase-related protein (PERK) [16].
IRE1 is activated during ER stress and splices invalid
mRNA, similar to yeast IRE1, into the mature X-box
binding protein 1 (XBP-1) mRNA, a bZIP-like tran-
scription factor [17–20]. XBP-1 is translated from the
spliced mRNA and is translocated to the nucleus to
regulate transcription of target genes. In addition,
IRE1 independently mediates the rapid degradation of
a specific subset of mRNAs due to their localization
on the ER membrane and to the amino-acid sequence
they encode [21]. This response could selectively halt
production of proteins that challenge the ER and
could make available the translocation and folding
machinery for the subsequent remodeling process. In
addition, IRE1 forms a trimeric complex with phos-
phorylated tumor necrosis factor receptor-associated
factor 2, apoptosis signal regulating kinase 1 and the

function of the ER transport machinery and defective
UPR signaling, resulting in diseases such as neurode-
generative disorders, diabetes, and endocrine defects
[11].
The UPR in plants is an important and constantly
expanding topic. However, study of the plant UPR is
a relatively new field, and its molecular details are only
now becoming clear. Recent developments in this field
will be explored in this review.
Transcriptional regulation of UPR
genes
The most prominent phenomenon induced by ER
stress is transcriptional regulation of UPR genes. The
induction of genes assumed to be related to the UPR
in plant cells has been reported. Binding protein (BiP)
is a representative UPR gene. BiP is induced in the
presence of drugs that cause ER stress, such as tunica-
mycin [38–45]. Tunicamycin inhibits UDP-N-acetyl-
glucosamine– dolichol phosphate N-acetylglucosamine-1-
phosphate transferase (GPT), such that the initial step
of the biosynthesis of dolichol-linked oligosaccharides
is blocked [46]. Treatment with tunicamycin results in
the inability of asparagine (N)-linked glycoproteins
synthesized in the ER to be glycosylated. Transgenic
Arabidopsis thaliana plants with a 10-fold higher level
of GPT activity were resistant to tunicamycin at a con-
centration that was lethal to control plants [44]. Like-
wise, transgenic plants grown in the presence of
tunicamycin have N-glycosylated proteins, and expres-
sion levels of BiP mRNA was lower than in control

identified. These genes were reanalyzed with functional
DNA microarrays using DNA clones from the fluid
microarray analysis. Together, 36 up-regulated genes
and two down-regulated genes in all samples treated
with the three drugs, tunicamycin, dithiothreitol or
azetidine-2-carboxylase were recognized as UPR genes.
The up-regulated UPR genes identified by the two
research groups are shown in Table 1, and include ER
chaperones, glycosylation ⁄ modification-related pro-
teins, translocon subunits, vesicle transport proteins,
and ER-associated degradation (ERAD) proteins.
Most of these proteins are orthologs of the genes iden-
tified as being related to the UPR in yeast and mam-
malian cells [1,30,51–54]. In addition, genes related to
the regulation of translation (P58
IPK
) [55] and apop-
tosis (BAX inhibitor 1) [56,57] were also identified as
being up-regulated during the UPR in plants [49,58].
Phospholipid biosynthetic enzymes increase in expres-
sion in the maize (Zea mays) floury-2 (fl-2) mutant
(described below) and soybean (Glycine max) suspen-
sion cultures when treated with tunicamycin [45], and,
in yeast, a number of lipid metabolism-related genes
are up-regulated by ER stress [1]. On the other hand,
neither of the DNA microarray analyses of the
Arabidopsis transcriptome described above detected
any up-regulation of lipid metabolism-related genes,
suggesting that additional experiments are needed to
assess if phospholipid metabolism-related genes are

these proteins also have a signal peptide. In mamma-
lian cells, expression of abundant genes is repressed
during ER stress depending on IRE1 but not on XBP-1.
Repression of these genes is fast compared with
expression changes mediated by XBP-1. Furthermore,
functional signal sequences of proteins encoded by
down-regulated genes are required for this repression
event to occur. Taken together, it is possible that
IRE1-mediated mRNA degradation occurs during co-
translational translocation [21]. The fact that more
than 80% of the encoded proteins in Arabidopsis with
down-regulated expression during ER stress have sig-
nal peptides raises the possibility that similar systems
may function in plant cells.
In both DNA microarray analyses, only the genes
that complied with certain restrictive criteria were
designated UPR genes, implying that some UPR genes
were missed during the analysis as a result of these cri-
teria. Thus, genes expressed at very low levels might
have been unintentionally eliminated from the analysis
because of difficulty in assessing differences in their
expression levels. For example, AtbZIP60, which was
not designated a UPR gene by DNA microarray ana-
lysis, is induced in response to ER stress as detected
by Northern blot and RT-PCR analyses [62]. It is
expected that genes identified by the DNA microarray
analyses will eventually be confirmed by other methods
such as mRNA quantification and promoter analysis.
A pivotal role of the UPR is to maintain ER home-
ostasis. Therefore, the presence of mutated proteins

At1g56340 Calreticulin 1 ERSE like 49
At1g09210 Calreticulin 2 ERSE like, XBP1-BS-like 48, 49
At4g24190 AtHsp90–7 ERSE like, XBP1-BS-like 48, 49
At2g47470 Similar to PDI ERSE like, XBP1-BS-like 48, 49
At1g77510 Similar to PDI ERSE like 49
At2g32920 Similar to PDI 48, 49
At1g04980 Similar to PDI ERSE like, XBP1-BS-like 49
At5g58710 AtCYP20-1 (cyclophilin ROC7) ERSE like, XBP1-BS-like 49
Glycosylation ⁄ modification
At2g02810 UDP-glucose ⁄ UDP-galactose transporter ERSE like 48, 49
At2g41490 UDP-GlcNAc:dolichol phosphate
N-acetylglucosamine-1-phosphate transferase
ERSE like 48, 49
At2g47180 Putative galactinol synthase XBP1-BS-like 48
At2g41490 GPT ERSE like, XBP1-BS-like 48
At4g15550 UDP-glucose indole-3-acetate
b-
D-glucosyltransferase
48
Translocation
At5g50460 SEC61 c subunit XBP1-BS-like 49
At1g29310 Similar to SEC61 a subunit ERSE like 49
At2g34250 Similar to SEC61 a subunit 49
At2g45070 Similar to SEC61 b subunit XBP1-BS-like 48, 49
At4g24920 Similar to SEC61 c subunit XBP1-BS-like 48, 49
At1g27330 Similar to SERP1 ⁄ RAMP4 ERSE like 49
At1g27350 Similar to SERP1 ⁄ RAMP4 ERSE like 48, 49
At3g51980 Similar to ER chaperone SIL 1 ERSE like, XBP1-BS-like 49
At5g03160 P58
IPK

protein bodies [64–70]. The increase in maize BiP
mRNA and corresponding protein concentrations
in mutants compared with those of wild-type maize
was endosperm-specific and inversely proportional to
changes in mutant zein synthesis [66]. The pattern of
gene expression in normal and the seven opaque
mutants o1, o2, o5, o9, o11, Mc and fl-2, protein syn-
thesis of which is the molecular basis of the mutation,
was assayed by profiling endosperm mRNA transcripts
with an Affymetrix GeneChip containing more than
1400 selected maize gene sequences [71]. Compared
with normal maize, alterations in the gene expression
patterns of the opaque mutants were pleiotropic, where
the expressions of BiP, protein disulfide isomerase
(PDI), calreticulin, GRP94 and cyclophilin, and other
physiological stress-related genes were increased in the
opaque mutants. The transcriptional response in fl-2
may be induced by the UPR, as the change in the
pattern of gene expression was restricted to the endo-
sperm in which the mutant a-zein was synthesized. The
expression pattern of o2 and fl-2 depends on the
molecular basis of the mutation. It remains necessary
to evaluate the relationship between the expression
patterns and the molecular basis of each mutation in
the other mutants before a complete understanding of
how these mutants affect ER homeostasis in plants will
be obtained.
Signal transduction during the UPR
Transcription of genes related to the UPR is controlled
by the specific transcription factor that binds to the

At5g59820 Zat12 48
Stress protein
At5g16660 HSP-like (D2T2) ERSE like 48
At1g67360 Putative stress-related protein XBP1-BS-like 48
Unclassified
At2g25110 Similar to stromal cell derived factor-2 48, 49
At5g09410 Similar to anther ethylene-up-regulated
calmodulin-binding protein ER1
ERSE like, XBP1-BS-like 49
At4g12720 Similar to growth factor protein with
mutT domain
48
At4g19880 GST ERSE like 48
At2g16060 Similar to AHB1 48
At4g26400 Putative ring zinc finger protein 48
At4g14430 Carnitine racemase-like protein ERSE like 48
At1g07670 ER-type calcium transporter ATPase 4 ERSE like, XBP1-BS-like 48
At5g39580 Peroxidase ATP24a 48
At4g10040 Cytochrome c ERSE like 48
a
Numbers in parentheses show the number of elements on the promoter.
Response to unfolded proteins in ER of plants R. Urade
1156 FEBS Journal 274 (2007) 1152–1171 ª 2007 The Author Journal compilation ª 2007 FEBS
of cis-acting regulatory elements that respond to ER
stress are known in mammals [11]. Among them, ER
stress response element (ERSE) and ERSE-II are tar-
gets for both ATF6 and XBP1 [15,77–79]. ATF6 is
constitutively synthesized as a type II transmembrane
protein in the ER [24]. When the ER-membrane-bound
precursors of ATF6 are cleaved by the serine protease

genome. Among them, only AtbZIP60, a factor that is
induced by treatment with tunicamycin, dithiothreitol
and azetidine-2-carboxylase, activates transcription
from P-UPRE and ERSE elements. The AtbZIP60
gene encodes a predicted type II transmembrane pro-
tein of 295 amino acids with an N-terminal bZIP
DNA-binding domain, a putative transmembrane
domain, and a 56-amino-acid small C-terminal domain
(Fig. 1A). A truncated form of AtbZIP60 lacking the
transmembrane domain (AtbZIP60 DC) fused with
green fluorescent protein (GFP) localized to the nuc-
leus. In other experiments, AtbZIP60 DC clearly acti-
vated both P-UPRE and ERSE-like sequences in a
dual luciferase assay using protoplasts of cultured
tobacco (Nicotiana tabacum) cells. Therefore, Atb-
ZIP60 is considered to be a transcription factor
responding to ER stress, where AtbZIP60 DC induces
the expression of AtbZIP60 through ERSE-like
sequences present in the promoter of AtbZIP60. In
contrast, wild-type AtbZIP60 is unable to activate
ERSE-like sequences and P-UPRE, probably because
it is anchored to the membrane. This suggests that
native AtbZIP60 may be released from the membrane
into the cytosol during ER stress to act as a transcrip-
tion factor in the nucleus (Fig. 2). In the Arabidopsis
genome, the At4g20310 gene encodes a membrane pro-
tein analogous to S2P, but it remains to be confirmed
whether AtbZIP60 is cleaved and released from the
membrane during ER stress. In addition, no conserved
sequence necessary for cleavage by S1P and S2P has

unclear whether it functions as a sensor for ER stress
in a manner similar to ATF6. Investigation into the
cellular localization of AtbZIP60 will probably clarify
these issues.
Orthologs of IRE1 have been identified in Arabidop-
sis (AtIre1-1 and AtIre1-2) and rice (Oryza sativa)
(OsIre1) [86–88]. Fusion proteins of AtIre1-1, AtIre1-2
or OsIre1 with GFP expressed in tobacco By2 cells
localize to the perinuclear ER. The expression patterns
of AtIre1-1 and AtIre1-2 have been examined with
fusion genes of their promoter and a reporter gene.
The expression of AtIre1-1 is restricted to certain tis-
sues at specific developmental stages such as the apical
meristem, the leaf margins where vascular bundles end,
the anthers before pollen is formed, the ovules at an
early stage of development, and the cotyledons imme-
diately after germination. AtIre1-2 is generally
expressed in plants. The C-terminal cytosolic domain
of IRE1ps is conserved among a variety of organisms
(Fig. 1B). The C-terminal halves of recombinant
AtIre1-2 and OsIre1 have autophosphorylation activ-
ity. When Lys442 of AtIre1-2 was mutated to Ala, this
activity was lost. The N-terminal luminal domains of
AtIre1-1, AtIre1-2 and OsIre1 function as ER stress
sensors in yeast cells, although the amino-acid
sequences of these N-terminal domains are dissimilar
from that of yeast IRE1. Thus, when chimeric genes
were created by fusing the N-terminal domains of
AtIre1-1, AtIre1-2 and OsIre1 with the C-terminal
domain of yeast IRE1, and were introduced into a

continuous throughout the entire plant by way of the
plasmodesmata network [95]. Certain stress signals,
such as an attack by a pathogen, are transmitted
throughout the plant, giving rise to systematic induc-
tion of specific genes through this continuity of the
ER. However, the UPR is restricted to the cells where
the stress was initiated and cannot induce a systemic
response in plants, as transcription of BiP mRNA was
found to be restricted to leaves treated with tunica-
mycin [96].
Enhancing cellular quality control
systems by the UPR
Folding
Folding of nascent polypeptides in cells is not as effi-
cient as was once thought. More than 30% of the nas-
cent polypeptides are assumed to be degraded as junk
products before being folded into their proper confor-
mation in the cytosol of animal cells [97]. Nascent
polypeptides produced in the ER are presumed to
undergo a similar fate. However, folding of polypep-
tides translocated into the ER lumen may fail more
often than that of the polypeptides in the cytosol
because these folding events require more complicated
steps such as glycosylation and ⁄ or formation of disul-
fide bonds. Therefore, the UPR is considered to be
weakly but constitutively activated and maintains the
homeostasis of the ER even in apparently unstressed
cells. In particular, developmental events associated
with high secretory activity are predicted to induce the
UPR [98,99]. The quality control of proteins includes

Peptidyl-prolyl-cis-trans isomerases (cyclophilin) survey
the status of the proline residues and rearrange them
from the cis to the trans form to ensure proper folding
of the nascent polypeptide chains. Twenty-nine genes
encoding cyclophilin family members are present in the
Arabidopsis genome, and five gene products are
assumed to be targeted to the ER lumen with N-ter-
minal signal peptides [107]. Among them, ATCYP20-1
is up-regulated during ER stress, and contains a
domain essential for peptidyl-prolyl-cis-trans isomerase
activity.
Four PDI-related genes are up-regulated during ER
stress. PDI catalyzes the formation and rearrangement
of disulfide bonds between correct pairs of Cys resi-
dues in nascent polypeptide chains in the ER [108].
PDI and related proteins are characterized by thiore-
doxin motifs within their primary structure [109,110];
Arabidopsis PDI-related proteins, the expression of
which is induced during ER stress, have two of these
motifs. A comprehensive search of the Arabidopsis gen-
ome identified 22 orthologs of known PDI-like pro-
teins [111]. PDI purified from plants or recombinant
PDI-related proteins expressed in Escherichia coli have
protein disulfide oxidoreductase activity [38,112–116],
and their importance in protein folding has been dem-
onstrated in rice endosperm [117]. In endosperm of rice
esp2 mutants lacking PDI, a precursor of the storage
protein proglutelin forms aggregates with other storage
proteins via interchain disulfide bonds within the
ER lumen, whereas in wild-type rice, proglutelins are

GlucNac
2
from a membrane-bound
dolichol phosphate anchor to consensus Asn-X-Ser ⁄
Thr residues in the polypeptide chain. The glucose resi-
dues on the transferred core glycan are sequentially
trimmed to Glc
1
Man
9
GlucNac
2
by b-glucosidase I and
b-glucosidase II. The monoglucosylated glycan on the
polypeptide chain is trapped by calnexin or calreticulin
to protect it from degradation, resulting in retention of
the polypeptide in the ER for folding [129,130].
The monoglucosylated form of the unfolded protein
shuttles through cycles of deglucosylation by b-glucosi-
dase II and reglucosylation by UDP-glucose–glycopro-
tein glucosyltransferase (UGGT), which preferentially
recognizes unfolded glucosylated glycoproteins [131]. This
process is called the calnexin ⁄ calreticulin cycle, and is
one arm of the quality control machinery in the mam-
malian ER. It is possible that interaction between
monoglucosylated N-glycan with calnexin ⁄ calreticulin
functions for the quality control of N-glycosylated pro-
teins in plants, although the calnexin ⁄ calreticulin cycle
remains to be elucidated in plants. However, circum-
stantial evidence supports the idea that the calnexin ⁄

transferase I, which catalyzes the first modification reac-
tion to the complex-type glycan [139].
UDP-glucose, the substrate for re-glucosylation of
N-glycan by UGGT, is synthesized in the cytosol, indi-
cating that a UDP-glucose transporter would be
required for the calnexin ⁄ calreticulin cycle. AtUTr1
from Arabidopsis is an ER-localized membrane pro-
tein, the expression of which is induced by treatment
with dithiothreitol [140], and is recognized as a UDP
galactose ⁄ glucose transporter [141]. In addition, up-
regulation of the ER chaperones, BiP and calnexin,
has been observed in an AtUTr1 insertional mutant,
suggesting that these plants may constitutively activate
the UPR. Taken together, it is possible that the calnex-
in ⁄ calreticulin cycle discriminates between folded and
unfolded glycoproteins in plant cells. In mammalian
cells, the recognition of the unfolded glycoproteins by
calnexin ⁄ calreticulin is coupled with the formation of
disulfide bonds, where the PDI-related thiol-oxidore-
ductase, ER-60 ⁄ ERp57, interacts with the P domain of
calnexin or calreticulin to fold N-glycosylated proteins
[142–144]. The amino-acid sequence of the P domain
of plant calnexin and calreticulin is highly conserved
compared with that of its mammalian counterparts
[145,146]. However, it is not known whether plant
calnexin or calreticulin cooperates with any plant PDI-
related oxidoreductase to form disulfide bonds in
N-glycosylated proteins.
Degradation of unfolded proteins
Unfolded proteins generated in the rough ER are

exported into the cytosol, deglycosylated, and degra-
ded by the proteasome [153,154]. A mutant of barley
(Hordeum vulgare) mildew resistance O protein-1 is
also degraded by UPS-dependent ERAD in plants
[155]. Individual mutant mildew resistance O protein-1
proteins with single amino-acid substitutions in its
seven-transmembrane domain exhibit markedly
reduced half-lives, are polyubiquitinated, and can be
stabilized through inhibition of proteasome activity.
When the mutant mildew resistance O protein-1 is
transfected into Arabidopsis plants previously transfected
with dominant negative mutants of the putative AAA
ATPase AtCDC48A ⁄ p97 (a component of the ERAD
machinery) [156,157], the degradation of the mutant
mildew resistance O protein-1 is impaired. This
strongly suggests that mildew resistance O protein-1 is
an endogenous substrate of a UPS-dependent ERAD-
related quality control mechanism in plants.
In plants, several misfolded proteins are translocated
across the ER membrane to the cytosol and degraded
by an unknown UPS-independent system. The C-ter-
minal extension mutant of phaseolin transfected into
tobacco protoplasts is degraded very rapidly in a bre-
feldin A- and proteasome inhibitor-insensitive manner
[158], suggesting that it is performed in a pre-Golgi
compartment, probably in the cytosol. Likewise, when
both endogenous and recombinant cell wall invertases
are synthesized without their N-glycans in BY2
tobacco cells, they both degrade very rapidly [159].
This degradation does not occur in an acidic com-

polypeptides to the ER lumen was reported by
Oyadomari et al. [166]. P58
IPK
associates with SEC61,
recruits HSP70 chaperones to the cytosolic face of
SEC61 and associates with translocating polypeptides
during ER stress. In P58
IPK
-knockout mice, cells with a
high secretory burden are markedly compromised in
their ability to cope with ER stress. On the basis of
these results, P58
IPK
is thought to be a key mediator
of cotranslocational ER protein degradation, and
probably contributes to ER homeostasis in stressed
cells.
Genes that stimulate vesicle transport from the ER
to the cis-Golgi are induced during ER stress in Ara-
bidopsis (Table 1). Among them, EMP24, SAR1B and
SEC23 are shown to make a complex with subunits of
the COPII coat, which are key molecules for export of
proteins from the ER, and promote transport of newly
synthesized proteins from the ER into ER subdomains
or Golgi in yeast [167–170]. Newly synthesized proteins
that do not fold correctly in the ER are targeted for
ERAD through distinct sorting mechanisms; soluble
luminal ERAD substrates require ER–Golgi transport
and retrieval for degradation, whereas transmembrane
ERAD substrates are retained in the ER [169].

a small, membrane-bound protein, the function of
which remains unclear, but its deletion abolishes
degradation of misfolded proteins in yeast [175].
Remarkably, maize DER1-like gene (Zm Derlins)is
capable of functionally complementing a yeast DER1
deletion mutant [176]. YOS9 is a member of the OS-9
protein family and shows similarity to mannose-6-
phosphate receptors. It is an essential component for
degradation of misfolded ER-luminal glycoproteins
[177], and specifically associates with misfolded ERAD
substrates [171].
ERAD is considered to be the primary disposal
route for unfolded and misfolded proteins, but grow-
ing evidence suggests a vacuolar role in protein quality
control. Even in plants, the vacuolar system is involved
in the degradation of misfolded proteins generated in
the ER. Pimpl et al. [178] demonstrated that BiP is
constitutively transported to the vacuole in a wortmannin-
sensitive manner in tobacco, and that it could play an
active role in this second disposal route for misfolded
proteins. ER export of BiP to the Golgi apparatus is
dependent on COPII. BiP is transported to the lytic
vacuole via multivesicular bodies, which represent the
plant prevacuolar compartment. When the plant is
treated with tunicamycin, a subset of BiP-unfolded
protein complexes is transported to the vacuole and
degraded. As this degradation process is very rapid,
the transported BiP–ligand complexes in the vacuole
are not detected under normal circumstances. When
the route from the Golgi apparatus to vacuoles is

to function as a feedback regulator of translation in
the later phase of ER stress. In Arabidopsis, the P58
IPK
gene is up-regulated and the phosphorylation of eIF2a
(Ser51) is partially inhibited by ER stress [49], but
translation as a whole is not affected. Induction of
Arabidopsis P58
IPK
and a subsequent decrease in phos-
phorylation of eIF2a (Ser51) may increase the transla-
tional efficiency of unidentified gene(s). Alternatively,
induction of P58
IPK
could be required for the cotrans-
locational degradation of ER proteins in an effort to
maintain the homeostasis of the ER as described
above.
The idea that programmed cell death (PCD) func-
tions during the UPR in plants is supported by several
lines of indirect evidence. van Doorn & Woltering
[181] categorized plant PCD into three morphological
types, including apoptotic-like PCD, autophagy, and
nonlysosomal PCD. In cultured sycamore (Acer pseudo-
platanus L) cells, treatment with tunicamycin induced
apoptotic PCD, as indicated by nuclear morphology
and DNA fragmentation [182,183]. In cultured soy-
Response to unfolded proteins in ER of plants R. Urade
1162 FEBS Journal 274 (2007) 1152–1171 ª 2007 The Author Journal compilation ª 2007 FEBS
bean cells, inhibition of ER-type IIA Ca
2+

marker for PCD [190,191]. Accumulation of Hsr203J
mRNA begins at 10 h and plateaus at 24 h after
treatment with tunicamycin, whereas accumulation of
BiP and PDI mRNA begins 2 h after treatment with
tunicamycin [185]. This suggests that transcription of
Hsr203J mRNA is induced by a signal-transduction
system different from the UPR governing the induc-
tion of molecular chaperones during ER stress. Taken
together, these data suggest that apoptotic PCD is
induced in plants when ER homeostasis is not restored
after stress.
Future perspectives
Plant ER is an extremely flexible and adaptable organ-
elle, which differentiates into various types of organelle
to cope with internal and external stresses and to con-
tain the enormous number of proteins that are actively
synthesized there [192–194]. Therefore, the UPR that is
unique to plants is expected to function widely,
although the molecular mechanisms underlying the
UPR system in plants, animals, and yeast share com-
mon components. This is supported by the fact that a
number of plant-specific genes are induced by ER
stress, but the functional significance of their induction
has not yet been established. Recent studies in yeast
and mammals have highlighted the importance of the
UPR in nutrient sensing and control of differentiation
[11,32,33]. In diploid yeast, nitrogen starvation inhibits
HAC1 splicing and induces pseudohyphal growth. As
this phenomenon is repressed in strains defective in the
UPR, the latter is thought to have an important

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