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1 P) cleavage from the autophagic reporter GFP-ATG8.
2 protein Atg11 and the ubiquitin-like protein Atg8.
3 ion, and mRNA levels of the autophagy marker ATG8.
4 plex, represses the essential autophagy gene ATG8.
5 ating autophagy through its interaction with Atg8.
6 cluding a five-member gene family expressing ATG8.
7 of each of these functions, ATG1, ATG6, and ATG8.
8 ORM1/2 derivatives that do not interact with ATG8.
9 with FLS2 and the autophagy-related protein ATG8.
10 formation through reversible modification of ATG8.
11 EXO70D AIM with the core autophagy protein, ATG8.
12 each subfamily as well as all six mammalian ATG8s.
13 obilization in cereals, we describe here the ATG8/12 conjugation cascades in maize (Zea mays) and exa
14 TG8 and ATG12, we previously showed that the ATG8/12 conjugation pathways together are important when
15 te either tag, we previously showed that the ATG8/12 conjugation system is important for survival und
16 s loci encoding all components necessary for ATG8/12 conjugation, including a five-member gene family
17 lyzed the conjugation machinery required for ATG8/12 modification in Arabidopsis thaliana with a focu
22 ring stress via the interaction of DSK2 with ATG8, a ubiquitin-like protein directing autophagosome f
24 patterns in in vitro extract assays, altered ATG8 accumulation levels, an altered pattern of GFP-ATG8
25 however, although we know that the amount of Atg8 affects the size of autophagosomes, the mechanism f
26 knockdown of autophagy proteins Atg7 and LC3/Atg8 also decreased mitochondrial fragmentation without
29 of these components leads to an increase in Atg8 and a concomitant increase in autophagic activity.
30 ation of the two ubiquitin-fold polypeptides ATG8 and ATG12 to phosphatidylethanolamine and the ATG5
31 jugation of two ubiquitin-like protein tags, ATG8 and ATG12, to phosphatidylethanolamine and the ATG5
32 TG7 E1 required to initiate ligation of both ATG8 and ATG12, we previously showed that the ATG8/12 co
33 ubiquitin-like protein conjugation systems, Atg8 and Atg16, to the phagophore assembly site is affec
34 en required for the efficient recruitment of Atg8 and Atg18 to the site of autophagosome formation an
35 Atg11 at the PAS enhances the recruitment of Atg8 and Atg9 to this site and facilitates the formation
36 COG genes resulted in the mislocalization of Atg8 and Atg9, which are critical components involved in
39 d upregulation of the phagolysosomal markers Atg8 and p62 was notably reduced in draper mutant flies.
41 er stress conditions to ensure lipidation of ATG8 and thus autophagy progression in C. reinhardtii.
43 teracting region (LIR) docking site (LDS) in ATG8s and LIR motifs in various interaction partners.
44 cascades that couple the AUTOPHAGY-RELATED8 (ATG8) and ATG12 proteins to their respective targets, ph
45 raction between autophagy-related protein 8 (Atg8) and fatty acid synthase (FAS), a pivotal enzymatic
46 homologue of yeast autophagy-related gene 8 (ATG8), and recruited it to stable microtubules in a MAP1
47 y co-localizes with the autophagosome marker ATG8, and anti-NAP1 identifies autophagosomes in immuno-
48 n of p300 reduces acetylation of Atg5, Atg7, Atg8, and Atg12, although overexpressed p300 increases t
49 sion of key autophagy proteins such as ATG7, ATG8, and receptor interacting protein (RIP) blocks ROS
57 on conjugation machinery in the SUMO, NEDD8, ATG8, ATG12, URM1, UFM1, FAT10, and ISG15 pathways while
60 onstrate that Atg1 is activated by lipidated Atg8 (Atg8-PE), stimulating substrate phosphorylation al
62 on via the binding of autophagy receptors to Atg8 (autophagy-related 8) family proteins on the autoph
65 enhance autophagy, while HopF3 also targets ATG8 but suppresses autophagy, with both effectors promo
66 tion that may confer specific binding to the Atg8-coated autophagosomal membrane on which Atg8 is con
67 s issue of Cell, Nakatogawa et al. show that Atg8 conjugated to PE mediates tethering between adjacen
71 TG13-deficient plants, but the biogenesis of ATG8-decorated autophagic bodies does not, indicating th
73 cumulation levels, an altered pattern of GFP-ATG8-decorated cellular structures, and altered recovery
78 ytosis by a murine macrophage cell line, and Atg8 expression was exhibited in WT C. neoformans during
79 ogenesis, a strain of C. neoformans in which Atg8 expression was knocked down by RNA interference was
80 esults clarify the essential function of the Atg8 family and identify GABARAP subfamily members as pr
83 knock-out mice, as did a mutant lacking the Atg8 family interacting motif (AIM) and another mutant t
84 c acid receptor-associated protein (GABARAP) Atg8 family is much less understood than the LC3 Atg8 fa
92 atg8ylation with LC3B, one of six mammalian ATG8 family proteins, has been viewed as the hallmark of
95 family is much less understood than the LC3 Atg8 family, and the relationship between the GABARAPs'
96 e effector PexRD54 binds potato ATG8 via its ATG8 family-interacting motif (AIM) and perturbs host-se
99 in the N terminus, a domain associated with ATG8-family-specific functions during autophagosome form
101 steine proteases are required for processing Atg8 for the latter to be conjugated to phosphatidyletha
103 ue to ATG4.2 having a key role in removal of ATG8 from mature autophagosomes and thus facilitating de
104 The loss of Atg21 results in the absence of Atg8 from the pre-autophagosomal structure (PAS), which
110 bly, whereas there are only one atg4 and one atg8 gene in the yeast, the mammals have four Atg4 homol
115 gment reduces coprecipitation with mammalian Atg8 homolog GABARAPL1, suggesting a direct interaction.
116 conjugation) to compare the ability of human ATG8 homologs (LC3, GABARAP, and GATE-16) to mediate mem
121 ole yeast Atg8 gene has six mAtg8 (mammalian Atg8) homologs, including the MAP1LC3 (microtubule-assoc
125 e in the lipidation of the human homologs of ATG8 (i.e., LC3 and homologs) on double membranes during
126 nts, that two additional sites interact with Atg8 in a LIR-like and thus mutually exclusive manner.
127 We show that Ape1 aggregates bind Atg19 and Atg8 in vitro; this could be used as a scaffold for an i
128 BIN2 phosphorylation of DSK2 flanking its ATG8 interacting motifs (AIMs) promotes DSK2-ATG8 intera
129 in its C terminus in addition to a canonical Atg8-interacting LC3-interacting region (LIR, with LC3 b
131 ATG8-binding proteins exploit a well-defined ATG8-interacting motif (AIM, or LC3-interacting region [
133 Rtn1 and Rtn2 interact with Atg8a using four Atg8-interacting motifs (AIMs) located at the C-terminus
136 he physiologically relevant AIM motif in the ATG8-interacting protein 2 (ATI-2) as well as the previo
138 two new closely related Arabidopsis thaliana Atg8-interacting proteins (ATI1 and ATI2) that are uniqu
142 ell-penetrating peptides that block the WSTF-ATG8 interaction do not affect acute inflammation but su
145 ATG8 interacting motifs (AIMs) promotes DSK2-ATG8 interaction, thereby targeting BES1 for degradation
146 tometry, we demonstrate that enhancing Bnip3-Atg8 interactions via phosphorylation-mimicked LIR mutat
148 he N-terminal beta-strand shapes the broader ATG8 interactor profiles, defining interaction specifici
157 a provide a rationale for Atg7 dimerization: Atg8 is transferred in trans from the catalytic cysteine
159 mutants, development of atg1-1, atg6(-), and atg8(-) is more aberrant in plaques on bacterial lawns t
161 protein fusion of the autophagosome marker, Atg8, is aberrant in both atg1-1 and atg6(-) mutants.
164 r findings are consistent with the view that ATG8 isoforms comprise a layer of specificity in the reg
167 ATG8 specialization by comparing two potato ATG8 isoforms using both in vivo protein interaction ass
170 he formation of autophagy-related 8-labeled (Atg8-labeled) vesicles and showed a dramatic attenuation
171 binding to the ubiquitin-like yeast protein Atg8 (LC3 in mammals), which is needed for autophagosome
172 nofluorescence for the autophagy protein LC3/Atg8, LC3 electrophoretic mobility shift, mitochondrial
176 sion to the autophagosome-associated protein Atg8/LC3 led to strongly enhanced MHC class II presentat
180 ase complex I (PI3KC3-C1) and conjugation of ATG8/LC3 proteins to phagophore membranes by the ATG12-A
182 Atg8/LC3 localization was analyzed after GFP-Atg8/LC3 transfection or with an Atg8/LC3 specific antis
183 in expression (i.e., Atg6/Beclin1, Atg7, and Atg8/LC3) and mitophagy protein Bnip3 expression in toni
184 lls, a subset of phagosomes gets coated with Atg8/LC3, a component of the molecular machinery of macr
185 s autophagosome expansion and recruitment of Atg8/LC3, potentially by decreasing the stability of Atg
186 of APP with the essential autophagy protein Atg8/LC3, which associates with preautophagosomal and au
187 3-phosphate, as well as on the lipidation of Atg8/LC3-like proteins, this area of research has recent
191 th the ubiquitin-like proteins (UBLs) of the Atg8/LC3/GABARAP family and adaptors, Atg11 (in yeasts)
192 complex including Sin3 and Rpd3 to regulate Atg8 levels; deletion of any of these components leads t
193 Using a GFP-tagged and a new tandem-tagged Atg8/LGG-1 reporter, we quantified autophagic vesicles a
197 reactivity toward errant nucleophiles, while Atg8 lipidation cascade enzymes induce E2 active site re
203 ble for localizing ATG12-5-16 L1 and driving ATG8 lipidation, whilst WIPI3 and 4 belong to a second W
205 nd human hosts, revealing that cross-kingdom ATG8-LIR/AIM associations can also be predicted by AF2-m
206 well known that the conjugation of mammalian ATG8s (mATG8s) to phosphatidylethanolamine (PE) is a key
208 e arrest with protein aggregate clearance by Atg8-mediated activation of the Nrf2-like transcription
209 on of the ATG12-ATG5 adduct is essential for ATG8-mediated autophagy in plants by promoting ATG8 lipi
211 thogen-encoded virulence factors that target ATG8 members in their plant and human hosts, revealing t
214 ing region (LIR, with LC3 being a homolog of Atg8) motif, but their mode of interaction with Atg8 is
219 olar satellites can specifically regulate an ATG8 ortholog, the centrosomal GABARAP reservoir, and ce
221 tophagy because in its absence the remaining ATG8 orthologs do not support efficient antibacterial au
224 the kinetics parameters of the various Atg4-Atg8 pairs provides a base for the understanding of the
225 ral core ATG genes, such as highly divergent ATG8 paralogs in dermatophytes and multiple ATG15 duplic
226 with a method that unequivocally detects the ATG8-PE adduct, we also show that ATG8 lipidation requir
227 tg18 and Atg21 facilitate the recruitment of Atg8-PE to the site of autophagosome formation and prote
228 te that Atg1 is activated by lipidated Atg8 (Atg8-PE), stimulating substrate phosphorylation along th
230 ssential for synthesizing the ATG12-ATG5 and ATG8-phosphatidylethanolamine adducts that are central t
232 quitin-like proteins (UBLs)-Atg5, Atg12, and Atg8-play in the formation of the double-membrane vesicl
233 LC3-interacting region (LIR) to traffic into ATG8-positive puncta that often initiate from three-way
234 survival and results in the accumulation of Atg8-positive structures at the vacuolar membrane, sugge
237 h CASM results in the lipidation of multiple ATG8 protein family members, we establish that LRRK2 lys
239 led by the amount of Atg8; thus, controlling Atg8 protein levels is one potential mechanism for modul
240 matic residue in Atg8 proteins, producing an Atg8 protein that could not be reconjugated by Atg7 and
242 phagic bodies and immunoblot analysis of the ATG8 protein to show that sulfide (and no other molecule
243 motes the accumulation and lipidation of the ATG8 protein, which is associated with the process of au
244 somal membrane by interacting with lipidated ATG8 proteins (LC3/GABARAP) that are intimately associat
246 n-dependent mitophagy, and cells lacking all ATG8 proteins accumulate cytoplasmic UB aggregates, whic
248 phagy proteins via an LIR motif to mammalian ATG8 proteins and, independently and via a discrete moti
250 l effector protein RavZ to directly uncouple Atg8 proteins attached to phosphatidylethanolamine on au
253 equent involvement of a conserved surface on ATG8 proteins known to interact with LC3-interacting reg
254 c activity and is responsible for processing Atg8 proteins near the carboxyl terminus, exposing a con
256 le has the ability to interact with multiple Atg8 proteins simultaneously, resulting in a high-avidit
258 iched in autophagosomes, and associated with ATG8 proteins that recruit cargo-receptor complexes into
259 art of the E3 ligase directing lipidation of ATG8 proteins, a process central to membrane atg8ylation
260 ULK2, ATG13 and FIP200 interacted with human ATG8 proteins, all with strong preference for the GABARA
261 ophila Atg1 interacted with their respective Atg8 proteins, demonstrating the evolutionary conservati
262 residue and an adjacent aromatic residue in Atg8 proteins, producing an Atg8 protein that could not
263 autophagy, including autophagy receptors and ATG8 proteins, thereby functioning as an "eat me" signal
265 To elucidate the molecular functions of the ATG8 proteins, we engineered cells lacking genes for eac
271 gy, including formation of multiple aberrant Atg8 puncta and drastically impaired autophagosome bioge
272 nown role of S177 phosphorylation in OPTN on ATG8 recruitment, TBK1-dependent phosphorylation on S473
273 sport as determined by localization of a YFP-ATG8 reporter and its vacuolar cleavage during nitrogen
274 response genes (sgkB, csbA, acbA, smlA, and atg8) resulted in altered drug sensitivity, implicating
277 ompted us to define the biochemical basis of ATG8 specialization by comparing two potato ATG8 isoform
280 if and adjacent C-terminal region as well as ATG8 subfamily-specific residues in the LIR docking site
282 ly induces the autophagy regulators ATG6 and ATG8, sustains ATP levels, and reduces ROS levels to del
283 this loop and is associated with attenuated ATG8 targeting in response to ionophores in primary muri
285 agy is, in part, controlled by the amount of Atg8; thus, controlling Atg8 protein levels is one poten
286 erization targets ATG4b-mediated cleavage of ATG8 to enhance autophagy, while HopF3 also targets ATG8
287 ed for the conjugation of Atg12 to Atg5, and Atg8 to phosphatidylethanolamine (PE), and is essential
289 a parallel pathway involving conjugation of ATG8 to single membranes (CASM) at endolysosomal compart
290 on pathway that attaches AUTOPHAGY-RELATED8 (ATG8) to phosphatidylethanolamine, which then coats emer
291 We have identified a negative regulator of ATG8 transcription, Ume6, which acts along with a histon
292 by complex molecular systems, including the ATG8 ubiquitin-like conjugation system and the ATG4 cyst
294 tans RXLR-type effector PexRD54 binds potato ATG8 via its ATG8 family-interacting motif (AIM) and per
296 determine the interface between PexRD54 and ATG8, we solved the crystal structure of potato ATG8CL i
298 eraction of the Atg12~Atg5-Atg16 complex and Atg8 with Atg19 is mutually exclusive, which may confer
299 nd ATG13 colocalize with each other and with ATG8, with ATG1 tethered to ATG8 via a canonical ATG8-in
300 ed for autophagosome biogenesis, loss of all Atg8s yields smaller autophagosomes and a slowed initial