(The FASEB Journal. 2002;16:635-641.)
© 2002 FASEB
Cytoplasmic peptide:N-glycanase (PNGase) in eukaryotic cells: occurrence, primary structure, and potential functions
TADASHI SUZUKI1,
HANGIL PARK2 and
WILLIAM J. LENNARZ3
Department of Biochemistry and Cell Biology and the Institute of Cell and Developmental Biology, State University of New York at Stony Brook, New York, USA
3Correspondence: E-mail: wlennarz{at}notes.cc.sunysb.edu
 |
ABSTRACT
|
|---|
A cytoplasmic peptide:N-glycanase has been implicated in the proteasomal degradation of newly synthesized misfolded glycoproteins exported from the endoplasmic reticulum. The gene encoding this enzyme (Png1p) has been identified in yeast. Based on sequence analysis, Png1p was classified as a member of the ‘transglutaminase-like superfamily’ that contains a putative catalytic triad of amino acids (cysteine, histidine, and aspartic acid). More recent studies in yeast indicate that Png1p can bind to the 26S proteasome through its interaction with the DNA repair protein Rad23p. A mouse homologue of Png1p (mPng1p) bound not only to the Rad23 protein, but also to various proteins related to ubiquitin and/or the proteasome through an extended amino-terminal domain. This NH2 terminus of mPng1p, which is not found in yeast, contains a PUB domain predicted to be involved in the ubiquitin-related pathway. This review will focus on the primary structure and potential functions of the cytoplasmic PNGases.—Suzuki, T., Park, H., Lennarz, W. J. Cytoplasmic peptide: N-glycanase (PNGase) in eukaryotic cells: occurrence, primary structure, and potential functions
Key Words: ERAD • endoplasmic reticulum • transglutaminase family
|
CYTOPLASMIC PEPTIDE:N-GLYCNASE (PNGase): OCCURRENCE IN NATURE
|
|---|
PNGase (also known as N-glycanase or glycoamidase; peptide-N4-(N-acetyl-ß-D-glucosaminyl)asparagine amidase; EC 3.5.1.52) hydrolyzes the ß-aspartylglycosylamine bond of asparagine-linked glycopeptides and glycoproteins (1
2
3
; Fig. 1
). This enzyme was first discovered in almond seeds (4)
and subsequently in bacteria (5)
. Because this enzyme can remove glycan moieties from glycoproteins under relatively mild conditions, it has been a powerful tool in analyzing the structure and biological functions of N-linked glycans on glycoproteins. The first animal PNGase activity was identified in fish embryos (6)
. The enzyme was active at acidic pH and believed to be of lysosomal origin (7)
. The acid PNGase from fish was proposed to act on a glycophosphoprotein, a major phosvitin-related egg yolk glycoprotein. The deglycosylation reaction catalyzed by acid PNGase was suggested to facilitate the degradation/absorption of glycophosphoprotein by the developing embryos (7
, 8)
.
View larger version (17K):
[in this window]
[in a new window]
|
Figure 1. Schematic representation of enzymatic reaction of peptide:N-glycanase (PNGase) acting on an asparagine-linked glycoprotein. PNGase catalyzes the scission of the bond between the proximal N-acetylglucosamine (GlcNAc) residue and the asparagine (Asn) residue to which it is linked, giving rise to an aspartic acid (Asp) -containing polypeptide chain and 1-amino-N-acetylglucosaminyl oligosaccharide. The latter is subsequently hydrolyzed nonenzymatically at physiological pH to generate N-acetylglucosaminyl oligosaccharide and ammonia.
|
|
PNGase activity in the cytoplasm was first described in mammalian cells (9
10
11
12)
and was found in hen oviduct (13)
, Medaka fish (7)
, and yeast (14)
. The ‘cytoplasmic’ PNGases are enzymatically quite different from PNGases found in plant, bacteria, and an acid PNGase in fish because they require an -SH group, a neutral pH for optimal activity, and unique carbohydrate binding properties (7
, 10
, 15
16
17)
. Although most activity was recovered in the cytosol fraction through subcellular fractionation studies (9
, 13
, 15)
, evidence has been presented for the occurrence of ‘membrane-associated’ PNGase activity (13
, 14
, 18)
with enzymatic properties similar to those of the soluble, cytoplasmic enzyme (13
, 14)
. Subcellular fractionation studies further demonstrated that the membrane-associated PNGase was in fact present in the endoplasmic reticulum (ER) -containing membrane fraction (13)
, suggesting that the membrane-associated form of PNGase might associate with the cytosolic face of the ER membrane.
|
INVOLVEMENT OF PNGase IN PROTEASOME-MEDIATED DEGRADATIONS
|
|---|
The initial expectation that cytoplasmic PNGase and its substrates (N-glycosylated proteins or peptides) localized to different subcellular compartments obscured understanding of the biological role of the enzyme. However, recent studies have clearly established that eukaryotic cells have an ‘ER-associated degradation’ (ERAD) system for catabolism of newly synthesized proteins (19)
. Sec61p is involved in the retro-translocation of misfolded proteins (28
29
30
; Fig. 2
). This process is conserved from yeast to humans, and recent evidence demonstrates that misfolded glycoproteins actually are retro-translocated from the ER into the cytosol, where the ubiquitin-proteasome pathway plays a central role in degrading these defective proteins (20
21
22
23
24
25
26
27
; Fig. 2
).
View larger version (45K):
[in this window]
[in a new window]
|
Figure 2. ER-associated degradation of a misfolded glycoprotein and proposed involvement of PNGase. (1) The protein that passes through the translocon (Sec61 channel) is N-glycosylated by oligosaccharyl transferase (OT); (2) the protein folds with the aid of various lumenal chaperones; (3) once the protein acquires the correct folding state, it exits the ER via vesicular transport; (4) however, if the protein cannot fold, it is dislocated (retrotranslocated) by the ‘dislocon’ (another channel involving Sec61p) out of the lumen of the ER into cytosol; (5) the protein is ubiquitinated (by the E2/E3 enzyme) and deglycosylated (by PNGase). The order of these events is currently unknown; for instance, there is no evidence that PNGase can act on ubiquitinated glycoproteins. The effect of oligosaccharide structure on PNGase action remains unclarified. (6) The protein is targeted for degradation by the action of the proteasome. Not all steps have been demonstrated for this pathway, especially the order in which steps (5) and (6) occur. Under physiological conditions, PNGase might act on glycoproteins or glycopeptides produced by proteasomal degradation (see text).
|
|
In 1996, Wiertz et al. reported that during the ER-associated degradation process of MHC class I heavy chain in human cytomegalovirus-infected cells, an intermediate de-N-glycosylated protein accumulated in the cytosol when an inhibitor of the proteasome was included. This observation strongly implicates the involvement of PNGase activity in the degradation process (28
, 31)
. Using either proteasome inhibitors or mutant cells with defects in proteasome activity, misfolded/unassembled substrates have so far been found to be de-N-glycosylated by PNGase in vivo in various organisms (Table 1)
. These results suggested that the PNGase-mediated de-N-glycosylation process might be widespread throughout eukaryotic cells.
|
IDENTIFICATION OF A GENE ENCODING CYTOPLASMIC PNGase IN YEAST
|
|---|
The potential importance of the PNGase-catalyzed reaction in the proteasomal degradation process had been proposed (13
, 14
, 28
, 31
32
33
34
35
36)
, but until recently it was impossible to test this hypothesis because of lack of information about the enzyme structure and specific inhibitors of its activity. However, the recent discovery of the gene encoding a cytoplasmic PNGase, PNG1, in Saccharomyces cerevisiae has opened the possibility of in-depth analysis of the precise function of this enzyme. PNG1 was identified by isolating a mutant defective in PNGase activity and subsequent mapping of the locus responsible for the loss of this activity (32)
. Using a GFP fusion construct, the enzyme (Png1p) was shown to be localized in the cytosol and nucleus (32)
. This observation was of particular interest because, unlike multicellular eukaryotes in which proteasomes are normally abundant in the cytosol, in S. cerevisiae the proteasome is concentrated at the nucleus (37
, 38)
.
|
PRIMARY STRUCTURE OF CYTOPLASMIC PNGases: MEMBERS OF THE TRANSGLUTAMINASE FAMILY
|
|---|
Comparison of the protein sequence of yeast Png1p with sequences in various databases revealed that this enzyme is highly conserved. Initially the occurrence of homologous proteins in mammalian cells, D. melanogaster, C. elegans, various fungi, and plants was demonstrated (32)
. Potential homologues were also found in Gallus gallus (gene accession no. BG711086), Xenopus laevis (BE491338), Danio rerio (zebrafish) (BG307395), and Oryzias latipes (Medaka fish) (AV668313) in an NCBI EST database, further confirming the wide distribution of this enzyme in vertebrates. S. cerevisiae and S. pombe Png1ps have a ‘core’ sequence that is highly homologous (37% identity; 53% similarity, 6% gaps between yeast Png1p and its human homologue). A key difference is that the homologues in higher eukaryotes, unlike yeast, have extended domains at both the amino and carboxyl termini of the core domain (32
; Fig. 3
). An interesting feature of the PNGases is the presence of a ‘transglutaminase’ motif in the most conserved region (57% identity and 69% similarity between yeast Png1p and human homologue); therefore, they have been proposed to be part of the transglutaminase-like superfamily (39
; Fig. 3
). Transglutaminase is an enzyme that establishes covalent links between proteins by formation of amide cross-links between the side chains of glutamate and lysine residues (39)
. Proteins in the transglutaminase family usually possess a putative catalytic triad consisting of cysteine, histidine, and aspartate residues that is similar to the catalytic triad of thiol proteases. Some proteins in this superfamily are believed to be proteases (39)
. Since the proteins in the transglutaminase superfamily are responsible for formation or hydrolysis of amide bonds, it is not surprising that the cytoplasmic PNGase (an amidase) was defined as a third type of enzyme belonging to this superfamily. Indeed, the potential catalytic triad in this domain is conserved in all Png1p homologues (Fig. 4
). Consistent with this idea, the png1–1 allele, which causes the defect in PNGase activity in yeast (32)
, was found to have a single amino acid substitution in which the putative catalytic histidine residue was changed to tyrosine (Fig. 4
, second asterisk). Reducing reagents such as dithiothreitol are required for in vitro enzyme activity of the cytoplasmic PNGases (10
, 13
, 14)
. This observation is consistent with the assumption that they have a cysteine residue that acts as a critical nucleophile for activity.
View larger version (25K):
[in this window]
[in a new window]
|
Figure 4. Catalytic residues conserved in cytoplasmic PNGase and a comparison of these with conserved residues of a transglutaminase (factor XIIIa; 37
). The putative catalytic triad residues (Cys, His, Asp) found in all the proteins are indicated with asterisks above the consensus sequence. The number shown within the factor XIIIa sequence represents the number of amino acid residues omitted from this figure for alignment of the carboxyl-terminal sequences containing a putative catalytic aspartate residue.
|
|
A novel sequence motif, the PUB domain, was recently identified in an amino-terminal region of vertebrate and D. melanogaster Png1p homologues (40
; Fig. 3
). This domain has also been found in proteins bearing an UBA (ubiquitin-associated) or UBX domain, both of which are found in various proteins implicated in ubiquitin-related pathway (40)
. The PUB domain is proposed to serve as a protein–protein interaction domain (40)
, since mouse Png1p can interact with variety of proteins through a region containing it (41
; see below).
|
POTENTIAL FUNCTION OF CYTOPLASMIC PNGase IN EUKARYOTES
|
|---|
Despite the ubiquitous distribution of highly conserved Png1p in eukaryotes, its precise function in cellular processes is not understood. In S. cerevisiae, deletion of PNG1 had no apparent effect on growth rate or viability under a variety of experimental conditions. In fact, some genes required for the ERAD process in yeast are nonessential and their deletions cause no detectable growth defects (23)
. These observations imply that the ERAD process may be dispensable at least under normal growth conditions in yeast. Two mechanisms regulate accumulation of unfolded proteins in the lumen of the ER: one is the unfolded protein response (UPR), which up-regulates proteins that facilitate correct folding of secretory proteins (42
43
44)
; the other is the previously mentioned ERAD (20–27; Fig. 2
). Studies have shown a tight coordination between the UPR and ERAD responses (45
46
47)
, which could explain the dispensability of ERAD in yeast under normal conditions. The ER-associated degradation process is known to be closely associated with genetic diseases in mammals (48)
.
Several observations support the idea that Png1p is involved in proteasome-mediated degradation. 1) In mammalian cells and yeast, small glycopeptides that follow a retrograde transport route similar to that of misfolded proteins (49
, 50)
are subsequently de-N-glycosylated in the cytosol by PNGase (12
, 14)
. 2) A decrease in the rate of degradation of a misfolded protein was observed in yeast in png1
cells (32)
. However, a direct link between formation of in vivo de-N-glycosylated protein intermediates and activation of Png1p has not been rigorously established in any system. Neither the biochemically purified mammalian cytoplasmic PNGase nor the purified yeast Png1p acts on intact glycoprotein substrates in vitro (12
, 32)
despite abundant evidence that this enzyme acts on glycoproteins in vivo (see Table1
). This puzzling observation may be analogous to the action of the isolated 20S catalytic proteasome subcomplex, which acts efficiently only on small peptide substrates in vitro. The proposed function of the 19S ATPases is to unwind protein substrates before their degradation by the 20S proteolytic complex (51
52
53)
. Perhaps unfolding of the substrate by a yet unknown cofactor is required before Png1p can degrade glycoproteins.
|
Rad23 PROTEIN (Rad23p) AS AN ESCORT PROTEIN THAT LINKS Png1p AND THE 26S PROTEASOME
|
|---|
Very recently the Rad23 protein was identified as a PNGase binding protein by two-hybrid screening in yeast (54)
. This observation may shed light on the still enigmatic functional and/or physical relationship between the cytoplasmic PNGase and the 26S proteasome. RAD23 was originally identified as a gene involved in nucleotide excision repair (55)
. Recent evidence showed that a fraction of the Rad23 protein (Rad23p) binds to 26S proteasome through the Rad23p NH2 terminus ubiquitin-like domain (56)
. In fact, the physical interaction of Png1p with the 26S proteasome occurs in a Rad23p-dependent manner in yeast, as assessed by coimmunoprecipitation analysis (54)
. Therefore, the association of Png1p with the 26S proteasome may produce a complex in which de-N-glycosylation and proteolysis of unfolded glycoprotein substrates could be accomplished efficiently. Furthermore, the formation of a Rad23p-Png1p complex was found to be distinct from the well-established Rad23p-Rad4p complex required for DNA repair (54)
. Png1p and Rad4p were predicted to share a common ‘transglutaminase fold’ (57)
. They were both found to bind the carboxyl-terminal domain of Rad23p, whereas Rad23p is known to be associated with the 26S proteasome through its amino-terminal domain (56
, 58)
. These observations may represent an ‘escort’ property of Rad23p that serves to connect the 26S proteasome with other proteins such as Png1p or Rad4p to regulate the biological functions of these binding proteins.
|
IDENTIFICATION OF PROTEINS THAT INTERACT WITH MOUSE Png1p
|
|---|
Because of the architectural difference between yeast Png1p and its mouse homologue (mPng1p; Fig. 3
), it was of interest to determine whether there are functional differences in these two proteins. A two-hybrid screening assay was used in an attempt to find proteins that bind to mPng1p. Several proteins (some implicated in the ubiquitin/proteasome pathway) were found to bind with mPng1p (41
; Table 2
). Those proteins include the mouse homologue of Rad23p (mHR23B), a 19S proteasome subunit S4, ubiquitin, a protein that has one UBA and one UBX domain, and autocrine motility factor receptor, which has a RING finger motif (59)
and a CUE domain (60)
, both of which are implicated in the ubiquitination reaction. This result was in sharp contrast to the case with yeast Png1p, where only Rad23p was identified as a binding protein (54)
. All interactions but that of Rad23p homologue required the amino-terminal domain of mPng1p (41)
. These results may display the evolutionary consequence of the addition of amino-terminal extension of mPng1p, including the PUB domain, which allows mPng1p to achieve various regulatory protein–protein interactions for the efficient glycoprotein degradation mediated by the proteasome.
View this table:
[in this window]
[in a new window]
|
Table 2. List of mouse Png1p-interacting proteins detected using the two-hybrid system (ref 41
and unpublished observations)a
|
|
|
UNANSWERED QUESTIONS
|
|---|
As discussed, compelling evidence has accumulated regarding the involvement of PNGase in proteasome-mediated degradation of newly synthesized proteins in the ER. Now that the genes encoding highly conserved cytoplasmic PNGases have been identified, rapid clarification of the precise function of PNGase is likely. Nevertheless, the following important questions remain to be answered. Are Png1p and its homologues responsible for accumulation of de-N-glycosylated intermediates? Or does Png1p function as a ‘peptide’:N-glycanase only after proteasome degradation of the polypeptide chain of misfolded glycoproteins occurs? If conditions are found whereby Png1p acts on glycoproteins in vivo, how is this activity regulated? Perhaps there is a component(s) that facilitates the deglycosylation of glycoproteins by cytoplasmic PNGases in vivo. A possible intrinsic ‘unfolding’ activity of PNGase has been hypothesized (36)
. Now that the physical interaction of Png1p and the 26S proteasome is evident, the 19S proteasome subunit obviously is one of the candidates that facilitate the unfolding of glycoprotein substrates because it has been shown to have an ‘unfoldase’ activity (51
52
53)
. Or it is possible that PNGase may be located in proximity to the ‘dislocon’, the site where protein is dislocated from the ER to the cytosol, so PNGase may be able to act on proteins that are already partially unfolded while they pass through the protein channel. Indeed, the lumenal (29
, 61
, 62)
and cytosolic chaperones (63
, 64)
are reported to be involved in degradation of ERAD substrates.
Another question regards the identity and biological function of the ‘membrane-associated’ form of the cytoplasmic PNGase. Is it actually the ER-associated PNGase that is anchored to the ER membrane? If so, how is this anchoring mediated? For ER-associated degradation, the ER-associated proteasome has been proposed to be important (36)
. The membrane-associated form of the PNGase might interact with the membrane-bound proteasome. This hypothesis then raises more interesting questions: How is the localization of PNGases regulated? Is it changed under the conditions in which the unfolding proteins accumulate? Note that heat-induced interaction of the 26S proteasome with the ubiquitin-conjugating E2 enzyme was reported recently (65)
. Whether an analogous regulation exists for the association of PNGase with the proteasome awaits determination. Finally, little is known about the biological function of Png1p homologues in higher eukaryotes, although a C. elegans strain mutated in Png1p has been identified in a screen for mutations that affect axon development and branching by an unknown mechanism (A. Colavita and M. Tessier-Lavigne, personal communication). Further studies should lead to a better understanding of the biological significance of the cytoplasmic PNGases in cellular processes.
|
ACKNOWLEDGMENTS
|
|---|
T.S. expresses sincere thanks to Drs. Yasuo and Sadako Inoue (Academia Sinica, Taipei) for their continuous encouragement and Mr. Michael A. Kwofie and Ms. Elizabeth Anderson-Till (SUNY at Stony Brook) for reading the manuscript. We thank Drs. Marc Tessier-Lavigne and Antonio Colavita (Stanford University) for communicating valuable information. We thank members of our lab for useful discussions and Ms. Lorraine Conroy for manuscript preparation. We are also grateful to Ms. Yuriditzi Pascacio-Montijo for preparation of the figures. This study was supported by National Institutes of Health grant GM33184 to W.J.L.
|
FOOTNOTES
|
|---|
1 Current address: PRESTO, JST (Japan Science and Technology Corporation), Department of Biophysics and Biochemistry, Graduate School of Sciences, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan. 
2 Current address: eXegenics, inc. 2110 Research Row, Dallas, TX 75235, USA.
|
REFERENCES
|
|---|
-
Takahashi, N. (1992) Glycoamidases. Takahashi, N. Muramatsu, T. eds. CRC Handbook of Endoglycosidases and Glycoamidases ,183-198 CRC Press Boca Raton, FL.
-
Tarentino, A. L., Plummer, T. H., Jr (1993) Deglycosylation of asparagine-linked glycans by PNGase F. Trends Glycosci. Glycotechnol. 5,163-170
-
Suzuki, T., Kitajima, K., Inoue, S., Inoue, Y. (1997) Occurrence and potential functions of N-glycanases. Gabius, H.-J. Gabius, S. eds. Glycosciences: Status and Perspectives ,121-131 Chapman & Hall GmbH. Weinheim, Germany.
-
Takahashi, N. (1977) Demonstration of a new amidase acting on glycopeptides. Biochem. Biophys. Res. Commun. 76,1194-1201[CrossRef][Medline]
-
Plummer, T. H., Jr, Elder, J. H., Alexander, S., Phelan, A. W., Tarentino, A. L. (1984) Demonstration of peptide:N-glycosidase F activity in endo-beta-N-acetylglucosaminidase F preparations. J. Biol. Chem. 259,10700-10704[Abstract/Free Full Text]
-
Seko, A., Kitajima, K., Inoue, Y., Inoue, S. (1991) Peptide:N-glycosidase activity found in the early embryos of Oryzias latipes (Medaka fish). The first demonstration of the occurrence of peptide:N-glycosidase in animal cells and its implication for the presence of a de-N-glycosylation system in living organisms. J. Biol. Chem. 266,22110-22114[Abstract/Free Full Text]
-
Seko, A., Kitajima, K., Iwamatsu, T., Inoue, Y., Inoue, S. (1999) Identification of two discrete peptide:N-glycanases in Oryzias latipes during embryogenesis. Glycobiology 9,887-895[Abstract/Free Full Text]
-
Inoue, S., Inoue, Y. (1997) Fish glycoproteins. Montreuil, J. Vliegenthart, J. F. G. Schachter, H. eds. Glycoproteins II ,143-161 Elsevier Amsterdam.
-
Suzuki, T., Seko, A., Kitajima, K., Inoue, Y., Inoue, S. (1993) Identification of peptide:N-glycanase activity in mammalian-derived cultured cells. Biochem. Biophys. Res. Commun. 194,1124-1130[CrossRef][Medline]
-
Suzuki, T., Seko, A., Kitajima, K., Inoue, Y., Inoue, S. (1994) Purification and enzymatic properties of peptide:N-glycanase from C3H mouse-derived L-929 fibroblast cells. Possible widespread occurrence of post-translational remodification of proteins by N-deglycosylation. J. Biol. Chem. 269,17611-17618[Abstract/Free Full Text]
-
Kitajima, K., Suzuki, T., Kouchi, Z., Inoue, S., Inoue, Y. (1995) Identification and distribution of peptide:N-glycanase (PNGase) in mouse organs. Arch. Biochem. Biophys. 319,393-401[CrossRef][Medline]
-
Römisch, K., Ali, B. R. S. (1997) Similar processes mediate glycopeptide export from the endoplasmic reticulum in mammalian cells and Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 94,6730-6734[Abstract/Free Full Text]
-
Suzuki, T., Kitajima, K., Emori, Y., Inoue, Y., Inoue, S. (1997) Site-specific de-N-glycosylation of diglycosylated ovalbumin in hen oviduct by endogenous peptide:N-glycanase as a quality control system for newly synthesized proteins. Proc. Natl. Acad. Sci. USA 94,6244-6249[Abstract/Free Full Text]
-
Suzuki, T., Park, H., Kitajima, K., Lennarz, W. J. (1998) Peptides glycosylated in the endoplasmic reticulum of yeast are subsequently deglycosylated by a soluble peptide:N-glycanase activity. J. Biol. Chem. 273,21526-21530[Abstract/Free Full Text]
-
Suzuki, T., Kitajima, K., Inoue, S., Inoue, Y. (1994) Does an animal peptide: N-glycanase have the dual role as an enzyme and a carbohydrate-binding protein?. Glycoconjugate J. 11,469-476[CrossRef][Medline]
-
Suzuki, T., Kitajima, K., Inoue, S., Inoue, Y. (1994) Occurrence and biological roles of ‘proximal glycanases’ in animal cells. Glycobiology 4,777-789[Abstract/Free Full Text]
-
Suzuki, T., Kitajima, K., Inoue, Y., Inoue, S. (1995) Carbohydrate-binding property of peptide:N-glycanase from mouse fibroblast L-929 cells as evaluated by inhibition and binding experiments using various oligosaccharides. J. Biol. Chem. 270,15181-15186[Abstract/Free Full Text]
-
Weng, S., Spiro, R. G. (1997) Demonstration of a peptide:N-glycosidase in the endoplasmic reticulum of rat liver. Biochem. J. 322,655-661
-
Klausner, R. D., Sitia, R. (1990) Protein degradation in the endoplasmic reticulum. Cell 62,611-614[CrossRef][Medline]
-
Kopito, R. R. (1997) ER quality control: the cytoplasmic connection. Cell 88,427-430[CrossRef][Medline]
-
Cresswell, P., Hughes, E. A. (1997) Protein degradation: the ins and outs of the matter. Curr. Biol. 7,R552-R555[CrossRef][Medline]
-
Suzuki, T., Yan, Q., Lennarz, W. J. (1998) Complex, two-way traffic of molecules across the membrane of the endoplasmic reticulum. J. Biol. Chem. 273,10083-10086[Free Full Text]
-
Plemper, R. K., Wolf, D. H. (1999) Retrograde protein translocation: ERADication of secretory proteins in health and disease. Trends Biochem. Sci. 24,266-270[CrossRef][Medline]
-
Brodsky, J. L., McCracken, A. A. (1999) ER protein quality control and proteasome-mediated protein degradation. Semin. Cell. Dev. Biol. 10,507-513[CrossRef][Medline]
-
Römisch, K. (1999) Surfing the Sec61 channel: bidirectional protein translocation across the ER membrane. J. Cell Sci. 112,4185-4191[Abstract]
-
Johnson, A. E., Haigh, N. G. (2000) The ER translocon and retrotranslocation: is the shift into reverse manual or automatic?. Cell 102,709-712[CrossRef][Medline]
-
Lord, J. M., Davey, J., Frigerio, L., Roberts, L. M. (2000) Endoplasmic reticulum-associated protein degradation. Semin. Cell Dev. Biol. 11,159-164[CrossRef][Medline]
-
Wiertz, E. J. H. J., Tortorella, D., Bogyo, M., Yu, J., Mothes, W., Jones, T. R., Rapoport, T. A., Ploegh, H. L. (1996) Sec61-mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction. Nature (London) 384,432-438[CrossRef][Medline]
-
Plemper, R. K., Bohmler, S., Bordallo, J., Sommer, T., Wolf, D. H. (1997) Mutant analysis links the translocon and BiP to retrograde protein transport for ER degradation. Nature (London) 388,891-895[CrossRef][Medline]
-
Pilon, M., Schekman, R., Römisch, K. (1997) Sec61p mediates export of a misfolded secretory protein from the endoplasmic reticulum to the cytosol for degradation. EMBO J. 16,4540-4548[CrossRef][Medline]
-
Wiertz, E. J. H. J., Jones, T. R., Sun, L., Bogyo, M., Geuze, H. J., Ploegh, H. L. (1996) The human cytomegalovirus US11 gene product dislocates MHC class I heavy chains from the endoplasmic reticulum to the cytosol. Cell 84,769-779[CrossRef][Medline]
-
Suzuki, T., Park, H., Hollingsworth, N., Sternglanz, R., Lennarz, W. J. (2000) PNG1, a yeast gene encoding a highly conserved peptide:N-glycanase. J. Cell Biol. 149,1039-1052[Abstract/Free Full Text]
-
Suzuki, T., Kitajima, K., Inoue, S., Inoue, Y. (1995) N-glycosylation/deglycosylation as a mechanism for the post-translational modification/remodification of proteins. Glycoconj. J. 12,183-193[CrossRef][Medline]
-
Shamu, C. E., Story, C. M., Rapoport, T. A., Ploegh, H. L. (1999) The pathway of US11-dependent degradation of MHC class I heavy chains involves a ubiquitin-conjugated intermediate. J. Cell Biol. 147,45-58[Abstract/Free Full Text]
-
Story, C. M., Furman, M. H., Ploegh, H. L. (1999) The cytosolic tail of class I MHC heavy chain is required for its dislocation by the human cytomegalovirus US2 and US11 gene products. Proc. Natl. Acad. Sci. USA 96,8516-8521[Abstract/Free Full Text]
-
Hirsch, C., Ploegh, H. L. (2000) Intracellular targeting of the proteasome. Trends Cell Biol. 10,268-272[CrossRef][Medline]
-
Enenkel, C., Lehmann, A., Kloetzel, P. M. (1998) Subcellular distribution of proteasomes implicates a major location of protein degradation in the nuclear envelope-ER network in yeast. EMBO J. 17,6144-6154[CrossRef][Medline]
-
Russell, S. J., Steger, K. A., Johnston, S. A. (1999) Subcellular localization, stoichiometry, and protein levels of 26 S proteasome subunits in yeast. J. Biol. Chem. 274,21943-21952[Abstract/Free Full Text]
-
Makorova, K. S., Aravind, L., Koonin, E. V. (1999) A superfamily of archaeal, bacterial, and eukaryotic proteins homologous to animal transglutaminases. Prot. Sci. 8,1714-1719[Abstract]
-
Suzuki, T., Park, H., Till, E. A., Lennarz, W. J. (2001) The PUB domain, a putative protein–protein interaction domain implicated in the ubiquitin-proteasome pathway. Biochem. Biophys. Res. Commun. 287,1083-1087[CrossRef][Medline]
-
Park, H., Suzuki, T., Lennarz, W. J. (2001) Identification of proteins that interact with mammalian peptide:N-glycanase and implicate this hydrolase in the proteasome-dependent pathway for protein degradation. Proc. Natl. Acad. Sci. USA 98,11163-11168[Abstract/Free Full Text]
-
Chapman, R., Sidrauski, C., Walter, P. (1998) Intracellular signaling from the endoplasmic reticulum to the nucleus. Annu. Rev. Cell Dev. Biol. 14,459-485[CrossRef][Medline]
-
Urano, F., Bertolotti, A., Ron, D. (2000) IRE1 and efferent signaling from the endoplasmic reticulum. J. Cell Sci. 113,3697-3702[Abstract]
-
Mori, K. (2000) Tripartite management of unfolded proteins in the endoplasmic reticulum. Cell 101,451-454[CrossRef][Medline]
-
Ng, D. T., Spear, E. D., Walter, P. (2000) The unfolded protein response regulates multiple aspects of secretory and membrane protein biogenesis and endoplasmic reticulum quality control. J. Cell Biol. 150,77-88[Abstract/Free Full Text]
-
Travers, K. J., Patil, C. K., Wodicka, L., Lockhart, D. J., Weissman, J. S., Walter, P. (2000) Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 101,249-258[CrossRef][Medline]
-
Casagrande, R., Stern, P., Diehn, M., Shamu, C., Osario, M., Zuniga, M., Brown, P. O., Ploegh, H. L. (2000) Degradation of proteins from the ER of S. cerevisiae requires an intact unfolded protein response pathway. Mol. Cell 5,729-735[CrossRef][Medline]
-
Aridor, M., Balch, W. E. (1999) Integration of endoplasmic reticulum signaling in health and disease. Nature Med. 5,745-751[CrossRef][Medline]
-
Römisch, K., Schekman, R. (1992) Distinct processes mediate glycoprotein and glycopeptide export from the endoplasmic reticulum in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 89,7227-7231[Abstract/Free Full Text]
-
Gillece, P., Pilon, M., Römisch, K. (1999) The protein translocation channel mediates glycopeptide export across the endoplasmic reticulum membrane. Proc. Natl. Acad. Sci. USA 97,4609-4614[Abstract/Free Full Text]
-
Braun, B. C., Glickman, M., Kraft, R., Dahlmann, B., Kloetzel, P.-M., Finley, D., Schmidt, M. (1999) The base of the proteasome regulatory particle exhibits chaperone-like activity. Nature Cell Biol. 1,221-226[CrossRef][Medline]
-
Strickland, E., Hakala, K., Thomas, P. J., DeMartino, G. (2000) Recognition of misfolding proteins by PA700, the regulatory subcomplex of the 26 S proteasome. J. Biol. Chem. 275,5565-5572[Abstract/Free Full Text]
-
Benaroudj, N., Goldberg, A. L. (2000) PAN, the proteasome-activating nucleotidase from archaebacteria, is a protein-unfolding molecular chaperone. Nature Cell Biol. 2,833-839[CrossRef][Medline]
-
Suzuki, T., Park, H., Kwofie, M. A., Lennarz, W. J. (2001) Rad23 provides a link between the Png1 deglycosylating enzyme and the 26 S proteasome in yeast. J. Biol. Chem. 276,21601-21607[Abstract/Free Full Text]
-
Prakash, S., Prakash, L. (2000) Nucleotide excision repair in yeast. Mutat. Res. 451,13-24[Medline]
-
Schauber, C., Chen, L., Tonganonkar, P., Vega, I., Lambertson, D., Potts, W., Madura, K. (1998) Rad23 links DNA repair to the ubiquitin/proteasome pathway. Nature (London) 391,715-718[CrossRef][Medline]
-
Anantharaman, V., Koonin, E. V., Aravind, L. (2001) Peptide-N-glycanases and DNA repair proteins, Xp-C/Rad4, are, respectively, active and inactivated enzymes sharing a common transglutaminase fold. Hum. Mol. Gen. 10,1627-1630[Abstract/Free Full Text]
-
Wang, Z., Wei, S., Reed, S. H., Wu, X., Svejstrup, J. Q., Feaver, W. J., Kornberg, R. D., Friedberg, E. C. (1997) The RAD7, RAD16, and RAD23 genes of Saccharomyces cerevisiae: requirement for transcription-independent nucleotide excision repair in vitro and interactions between the gene products. Mol. Cell. Biol. 17,635-643[Abstract]
-
Joazeiro, C. A., Weissman, A. M. (2000) RING finger proteins: mediators of ubiquitin ligase activity. Cell 102,549-552[CrossRef][Medline]
-
Ponting, C. P. (2000) Proteins of the endoplasmic-reticulum-associated degradation pathway: domain detection and functional prediction. Biochem. J. 351,527-535
-
Chillarón, J., Haas, I. G. (2000) Dissociation from BiP and retrotranslocation of unassembled immunoglobulin light chains are tightly coupled to proteasome activity. Mol. Biol. Cell 11,217-226[Abstract/Free Full Text]
-
Nishikawa, S., Fewell, S. W., Kato, Y., Brodsky, J. L., Endo, T. (2001) Molecular chaperones in the yeast endoplasmic reticulum maintain the solubility of proteins for retrotranslocation and degradation. J. Cell Biol. 153,1061-1069[Abstract/Free Full Text]
-
Gusarova, V., Caplan, A. J., Brodsky, J. L., Fisher, E. A. (2001) Apoprotein B degradation in promoted by the molecular chaperons hsp90 and hsp70. J. Biol. Chem. 276,24891-24900[Abstract/Free Full Text]
-
Zhang, Y., Nijbroek, G., Sullivan, M. L., McCracken, A. A., Watkins, S. C., Michaelis, S., Brodsky, J. L. (2001) Hsp70 molecular chaperone facilitates endoplasmic reticulum-associated protein degradation of cystic fibrosis transmembrane conductance regulator in yeast. Mol. Biol. Cell 12,1303-1314[Abstract/Free Full Text]
-
Tongaonkar, P., Chen, L., Lambertson, D., Ko, B., Madura, K. (2000) Evidence for an interaction between ubiquitin-conjugating enzymes and the 26S proteasome. Mol. Cell. Biol. 20,4691-4698[Abstract/Free Full Text]
-
Hughes, E. A., Hammond, C., Cresswell, P. (1997) Misfolded major histocompatibility complex class I heavy chains are translocated into the cytoplasm and degraded by the proteasome. Proc. Natl. Acad. Sci. USA 94,1896-1901[Abstract/Free Full Text]
-
Halaban, R., Cheng, E., Zhang, Y., Moellmann, G., Hanlon, D., Michalak, M., Setaluri, V., Hebert, D. N. (1997) Aberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme and contributes to the dedifferentiated phenotype of amelanotic melanoma cells. Proc. Natl. Acad. Sci. USA 94,6210-6215[Abstract/Free Full Text]
-
Mosse, C., Meadows, L., Luckey, C. J., Kittlesen, D. J., Huczko, E. L., Slingluff, C. L., Shabanowitz, J., Hunt, D. F., Engelhard, V. H. (1998) The class I antigen-processing pathway for the membrane protein tyrosinase involves translation in the endoplasmic reticulum and processing in the cytosol. J. Exp. Med. 187,37-48[Abstract/Free Full Text]
-
Huppa, J. B., Ploegh, H. L. (1997) The alpha chain of the T cell antigen receptor is degraded in the cytosol. Immunity 7,113-122[CrossRef][Medline]
-
Yu, H., Kaung, G., Kobayashi, S., Kopito, R. R. (1997) Cytosolic degradation of T-cell receptor alpha chains by the proteasome. J. Biol. Chem. 272,20800-20804[Abstract/Free Full Text]
-
de Virgilio, M., Weninger, H., Ivessa, N. E. (1998) Ubiquitination is required for the retro-translocation of a short-lived luminal endoplasmic reticulum glycoprotein to the cytosol for degradation by the proteasome. J. Biol. Chem. 273,9734-9743[Abstract/Free Full Text]
-
Bebök, Z., Mazzochi, C., King, S. A., Hong, J. S., Sorscher, E. J. (1998) The mechanism underlying cystic fibrosis transmembrane conductance regulator transport from the endoplasmic reticulum to the proteasome includes Sec61beta and a cytosolic, deglycosylated intermediary. J. Biol. Chem. 273,29873-29878[Abstract/Free Full Text]
-
Johnston, J. A., Ward, C. L., Kopito, R. R. (1998) Aggresomes: a cellular response to misfolded proteins. J. Cell Biol. 143,1883-1898[Abstract/Free Full Text]
-
Mancini, R., Fagioli, C., Fra, A. M., Maggioni, C., Sitia, R. (2000) Degradation of unassembled soluble Ig subunits by cytosolic proteasomes: evidence that retrotranslocation and degradation are coupled events. FASEB J. 14,769-778[Abstract/Free Full Text]
-
Petäjä-Repo, U. E., Hogue, M., Laperriere, A., Bhalla, S., Walker, P., Bouvier, M. (2001) Newly synthesized human delta opioid receptors retained in the endoplasmic reticulum are retrotranslocated to the cytosol, deglycosylated, ubiquitinated, and degraded by the proteasome. J. Biol. Chem. 276,4416-4423[Abstract/Free Full Text]
-
Simpson, J. C., Roberts, L. M., Römisch, K., Davey, J., Wolf, D. H., Lord, J. M. (1999) Ricin A chain utilises the endoplasmic reticulum-associated protein degradation pathway to enter the cytosol of yeast. FEBS Lett. 459,80-84[CrossRef][Medline]
-
Di Cola, A., Frigerio, L., Lord, J. M., Ceriotti, A., Roberts, L. M. (2001) Ricin A chain without its partner B chain is degraded after retrotranslocation from the endoplasmic reticulum to the cytosol in plant cells. Proc. Natl. Acad. Sci. USA 98,14726-14731[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
H. Nishitoh, H. Kadowaki, A. Nagai, T. Maruyama, T. Yokota, H. Fukutomi, T. Noguchi, A. Matsuzawa, K. Takeda, and H. Ichijo
ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1
Genes & Dev.,
June 1, 2008;
22(11):
1451 - 1464.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Shapira, D. Charuvi, Y. Elkabetz, K. Hirschberg, and S. Bar-Nun
Distinguishing between retention signals and degrons acting in ERAD
J. Cell Sci.,
December 15, 2007;
120(24):
4377 - 4387.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kato and Y. Kamiya
Structural views of glycoprotein-fate determination in cells
Glycobiology,
October 1, 2007;
17(10):
1031 - 1044.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hagihara, A. Miyazaki, I. Matsuo, A. Tatami, T. Suzuki, and Y. Ito
Fluorescently labeled inhibitor for profiling cytoplasmic peptide:N-glycanase
Glycobiology,
October 1, 2007;
17(10):
1070 - 1076.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Kuokkanen, W. Smith, M. Makinen, H. Tuominen, M. Puhka, E. Jokitalo, S. Duvet, T. Berg, and P. Heikinheimo
Characterization and subcellular localization of human neutral class II{alpha}-mannosidase cytosolic enzymes/free oligosaccharides/glycosidehydrolase family 38/M2C1/N-glycosylation
Glycobiology,
October 1, 2007;
17(10):
1084 - 1093.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kato, A. Kawahara, H. Ashida, and K. Yamamoto
Unique Peptide:N-glycanase of Caenorhabditis elegans has Activity of Protein Disulphide Reductase as well as of Deglycosylation
J. Biochem.,
August 1, 2007;
142(2):
175 - 181.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Suzuki, I. Hara, M. Nakano, G. Zhao, W. J. Lennarz, H. Schindelin, N. Taniguchi, K. Totani, I. Matsuo, and Y. Ito
Site-specific Labeling of Cytoplasmic Peptide:N-Glycanase by N,N'-Diacetylchitobiose-related Compounds
J. Biol. Chem.,
August 4, 2006;
281(31):
22152 - 22160.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Li, G. Zhao, X. Zhou, H. Schindelin, and W. J. Lennarz
The AAA ATPase p97 links peptide N-glycanase to the endoplasmic reticulum-associated E3 ligase autocrine motility factor receptor
PNAS,
May 30, 2006;
103(22):
8348 - 8353.
[Abstract]
[Full Text]
[PDF]
|
|
|
TOP
ABSTRACT
CYTOPLASMIC PEPTIDE:N-GLYCNASE...
