Binding Features and Functions of ATG3

Fang, Dongmei; Xie, Huazhong; Hu, Tao; Shan, Hong; Li, Min

doi:10.3389/fcell.2021.685625

Cited by 36 publications

(27 citation statements)

References 108 publications

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“…The cohort of autophagy-related (ATG) proteins regulating conventional autophagy, ATG3, ATG5, ATG7 and ATG10 (essential core proteins required for LC3A lipidation) [ 41 , 42 ] were more significantly expressed in the EUG treatments compared to the SPD treatment alone ( Figure 5 A,B). ATG13 involved in both the initiation stage (induction of the ULK1 complex) as well as the autophagosome–lysosome fusion stage [ 43 ], was equally expressed in all three treatments ( Figure 5 A,B).…”

Section: Resultsmentioning

confidence: 99%

“…Comparable effects were noted between EUG and SPD alone for ATG3, ATG4A, ATG4B, ATG13 and Beclin-1. Given numerous recent reports on SPD stimulation of autophagy [ 11 , 21 , 22 , 23 ], the effect of EUG can likewise be considered significant, based on the increased expression of several crucial core proteins at all stages of autophagic flux: initiation (ATG13) [ 43 ]; nucleation (Beclin-1) [ 11 ]; autophagasome elongation (ATG3, ATG5 and ATG7) [ 41 , 42 ] and autophagosome-lysosome fusion (Beclin-1; ATG13) [ 11 , 53 ]. Interestingly, increased ATG3, responsible for linking LC3-I to PE, with the help of the ATG12–ATG5 conjugate [ 42 ], has also been shown to been inversely associated with apoptopic-inducing caspase-8 expression, placing ATG3 as a novel link between apoptosis and autophagy [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

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Wheat Germ Spermidine and Clove Eugenol in Combination Stimulate Autophagy In Vitro Showing Potential in Supporting the Immune System against Viral Infections

et al. 2022

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Impaired autophagy, responsible for increased inflammation, constitutes a risk factor for the more severe COVID-19 outcomes. Spermidine (SPD) is a known autophagy modulator and supplementation for COVID-19 risk groups (including the elderly) is recommended. However, information on the modulatory effects of eugenol (EUG) is scarce. Therefore, the effects of SPD and EUG, both singularly and in combination, on autophagy were investigated using different cell lines (HBEpiC, SHSY5Y, HUVEC, Caco-2, L929 and U937). SPD (0.3 mM), EUG (0.2 mM) and 0.3 mM SPD + 0.2 mM EUG, significantly increased autophagy using the hallmark measure of LC3-II protein accumulation in the cell lines without cytotoxic effects. Using Caco-2 cells as a model, several crucial autophagy proteins were upregulated at all stages of autophagic flux in response to the treatments. This effect was verified by the activation/differentiation and migration of U937 monocytes in a three-dimensional reconstituted intestinal model (Caco-2, L929 and U937 cells). Comparable benefits of SPD, EUG and SPD + EUG in inducing autophagy were shown by the protection of Caco-2 and L929 cells against lipopolysaccharide-induced inflammation. SPD + EUG is an innovative dual therapy capable of stimulating autophagy and reducing inflammation in vitro and could show promise for COVID-19 risk groups.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Wheat Germ Spermidine and Clove Eugenol in Combination Stimulate Autophagy In Vitro Showing Potential in Supporting the Immune System against Viral Infections

et al. 2022

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“…We next studied another autophagy related gene, ATG3, which is important for autophagosome formation [ 21 ]. We calculated the correlation coefficient between HIF-1α and ATG3 expression using Pearson correlation analysis based on TCGA data, which indicated that HIF-1α expression correlated significantly and positively with ATG3 expression (Fig.…”

Section: Resultsmentioning

confidence: 99%

Eukaryotic initiation factor 5A2 mediates hypoxia-induced autophagy and cisplatin resistance

Chen

et al. 2022

Cell Death Dis

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Hypoxia-induced cisplatin resistance is a major challenge during non-small cell lung cancer (NSCLC) treatment. Based on previous studies, we further explored the effect of eukaryotic initiation factor 5A2 (eIF5A2) in hypoxia-induced cisplatin resistance. In this study, we found that autophagy and cisplatin resistance were increased under hypoxic conditions in three different NSCLC cell lines. Compared with that under normoxic conditions, dramatic upregulation of eIF5A2 and hypoxia inducible factor 1 subunit alpha (HIF-1α) levels were detected under hypoxia exposure. Small interfering RNA silencing of HIF-1α resulted in decreased expression of eIF5A2, indicating that eIF5A2 acts downstream of HIF-1α. In addition, the expression of eIF5A2 was significantly higher in NSCLC tumors compared with that in normal tissues. RNA silencing-mediated downregulation of eIF5A2 decreased hypoxia-induced autophagy, thereby reducing hypoxia-induced cisplatin resistance in NSCLC cells. The roles of eIF5A2 in cisplatin resistance were further validated in vivo. Combined treatment using eIF5A2-targeted downregulation together with cisplatin significantly inhibited tumor growth compared with cisplatin alone in the subcutaneous mouse model. In conclusions, eIF5A2 overexpression is involved in hypoxia-induced autophagy during cisplatin resistance. We suggest that a combination of eIF5A2 targeted therapy and cisplatin chemotherapy is probably an effective strategy to reverse hypoxia-induced cisplatin resistance and inhibit NSCLC development.

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“…Atg8-PE recognizes the Atg8-family interacting motif in cargos and promotes autophagosome biogenesis to result in autophagy-mediated degradation [ 26 ]. In the process of autophagy, ATG3 acts as an E2 ubiquitin-like conjugating enzyme in the ATG8 binding system, helping to extend the phagocytic cells [ 27 ]. The combination of ATG12 and ATG3 regulates mitochondrial homeostasis and cell death [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

Evaluating the Mode of Antifungal Action of Heat-Stable Antifungal Factor (HSAF) in Neurospora crassa

Liu

Jiang

Sun

et al. 2022

JoF

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Heat-stable antifungal factor (HSAF) isolated from Lysobacter enzymogenes has shown a broad-spectrum of antifungal activities. However, little is known about its mode of action. In this study, we used the model filamentous fungus Neurospora crassa to investigate the antifungal mechanism of HSAF. We first used HSAF to treat the N. crassa strain at different time points. Spore germination, growth phenotype and differential gene expression analysis were conducted by utilizing global transcriptional profiling combined with genetic and physiological analyses. Our data showed that HSAF could significantly inhibit the germination and aerial hyphae growth of N. crassa. RNA-seq analysis showed that a group of genes, associated with cell wall formation and remodeling, were highly activated. Screening of N. crassa gene deletion mutants combined with scanning electron microscopic observation revealed that three fungal cell wall integrity-related genes played an important role in the interaction between N. crassa and L. enzymogens. In addition, Weighted Gene Co-Expression Network Analysis (WGCNA), accompanied by confocal microscopy observation revealed that HSAF could trigger autophagy-mediated degradation and eventually result in cell death in N. crassa. The findings of this work provided new insights into the interactions between the predatory Lysobacter and its fungal prey.

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Binding Features and Functions of ATG3

Cited by 36 publications

References 108 publications

Wheat Germ Spermidine and Clove Eugenol in Combination Stimulate Autophagy In Vitro Showing Potential in Supporting the Immune System against Viral Infections

Wheat Germ Spermidine and Clove Eugenol in Combination Stimulate Autophagy In Vitro Showing Potential in Supporting the Immune System against Viral Infections

Eukaryotic initiation factor 5A2 mediates hypoxia-induced autophagy and cisplatin resistance

Evaluating the Mode of Antifungal Action of Heat-Stable Antifungal Factor (HSAF) in Neurospora crassa

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