LC3/GABARAP family proteins: autophagy‐(un)related functions

Schaaf, Marco B.E.; Keulers, Tom G.; Vooijs, Marc; Rouschop, Kasper M.A.

doi:10.1096/fj.201600698r

Cited by 509 publications

(423 citation statements)

References 133 publications

Supporting

Mentioning

382

Contrasting

Unclassified

Order By: Relevance

“…The above results showed that autophagy contributes to LPS-induced cytokine production and AS's anti-inflammation effect; therefore, the influence of AS on autophagyrelated molecules was tested, and markers such as the conversion of LC3B-I to LC3B-II, the accumulation of ATG5 and degradation of sequestosome 1 (SQSTM1), were selected to evaluate autophagy activity [18]. Western blotting showed that LPS induced an increase in LC3B-II and ATG5 levels for up to 1 h, and their levels began to decrease after 2 h in both RAW264.7 cells and BMDMs (Fig.…”

Section: As Inhibits Lps-stimulated Autophagic Activation Of Macrophagesmentioning

confidence: 99%

Artesunate Attenuates Pro-Inflammatory Cytokine Release from Macrophages by Inhibiting TLR4-Mediated Autophagic Activation via the TRAF6-Beclin1-PI3KC3 Pathway

Kuang

Cen

Qin

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Lipopolysaccharide (LPS) plays a critical role in excessive inflammatory cytokine production during sepsis. Previously, artesunate (AS) was reported to protect septic mice by reducing LPS-induced pro-inflammatory cytokine release. In the present study, the possible mechanism of the anti-inflammatory effect of AS was further investigated. Methods: An enzyme-linked immunosorbent assay was used to detect TNF-α and IL-6 release from macrophages. Specific small interfering RNAs (siRNAs) were used to knockdown the mRNA expression of target genes. Transmission electron microscopy and laser confocal microscopy were used to observe changes in autophagy. Western blotting was performed to detect the protein levels of tumor necrosis factor receptor-associated factor6 (TRAF6), Beclin1, phosphatidylinositol 3-kinase class III (PI3KC3), autophagy-related protein 5 (ATG5), and sequestosome 1. Immunoprecipitation (IP) and fluorescent co-localization were used to detect the interactions between TRAF6–Beclin1 and Beclin1–PI3KC3, and the ubiquitination of Beclin1. Results: AS inhibited TNF-α and IL-6 release from RAW264.7 cells, mouse bone marrow-derived monocytes (BMDMs) and peritoneal macrophages (PMs) induced by LPS. However, the inhibition by AS of LPS-induced cytokine release decreased when autophagy was inhibited using 3-MA, bafilomycin A1, or a siRNA targeting the Atg5 gene. Notably, AS showed an inhibition of LPS-induced autophagic activation not degradation. Whereas, these effects of AS were lost in macrophages lacking TLR4 and decreased in macrophages with down-regulated TRAF6, indicating that AS inhibited LPS-induced cytokine release and autophagic activation via TLR4-TRAF6 signaling. Western blotting results showed AS could reduce the levels of TRAF6, Beclin1, and PI3KC3. Importantly, the IP results showed AS only inhibited K63-linked ubiquitylation not total ubiquitylation of Beclin1 by acting on TRAF6. This interrupted the TRAF6–Beclin1 interaction and subsequent the formation of Beclin1– PI3KC3 core complex of the PI3K-III complex. Conclusion: AS inhibited LPS-induced cytokine release from macrophages by inhibiting autophagic activation. This effect was tightly related to blockade of the TRAF6-Beclin1-PI3KC3 pathway via decreasing K63-linked ubiquitination of Beclin1 and then interrupting the formation of Beclin1-PI3KC3 core complex of the PI3K-III complex. Our findings reveal the mechanism of AS’s anti-inflammatory effect and is significant for future targeted investigations of sepsis treatment.

show abstract

Section: As Inhibits Lps-stimulated Autophagic Activation Of Macrophagesmentioning

confidence: 99%

Artesunate Attenuates Pro-Inflammatory Cytokine Release from Macrophages by Inhibiting TLR4-Mediated Autophagic Activation via the TRAF6-Beclin1-PI3KC3 Pathway

Kuang

Cen

Qin

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…We found a strong positive correlation between LCPAT1 and LC3B . Since high expression of LC3B indicates increased autophagy 17 , we speculate that LCPAT1 may promote autophagy in lung cancer. We investigated the role of LCPAT1 in autophagy by knocking down LCPAT1 expression in tumor cells and assessing its impact on autophagy in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 89%

“…Microtubule-associated protein 1 light chain 3 beta ( LC3B ) levels increase and LC3B -encoded LC3-I is converted to LC3-II which accumulates and adsorbs on the autophagosome membrane. The degradation of p62 and increase of LC3-II are commonly used as markers of autophagy 17 . …”

Section: Introductionmentioning

confidence: 99%

Knockdown of long non-coding RNA LCPAT1 inhibits autophagy in lung cancer

Lin

et al. 2018

Cancer Biology & Medicine

View full text Add to dashboard Cite

Objective:Long non-coding RNAs (lncRNAs) are involved in numerous biological processes in lung cancer cells. In our previous studies, we identified a lncRNA, ENST00000439577, which is highly expressed in lung carcinomas, and termed it lung cancer progression-associated transcript 1 (LCPAT1). To characterize the role of LCPAT1 in lung cancer, we conducted the current study. Methods:Expression of LCPAT1 and autophagy-associated markers in tumor tissues and lung cancer cell lines was determined by real-time quantitative polymerase chain reaction (qPCR). Hematoxylin and eosin (HE) staining, qPCR, Western blot, and immunohistochemistry were performed to evaluate xenografted tumor tissues. Autophagy induced by rapamycin was detected by Western blot and immunofluorescence in lung cancer cell lines. Results:Expression of LCPAT1 and microtubule-associated protein 1 light chain 3 beta (LC3B) was positively correlated in lung cancer. Knockdown of LCPAT1 inhibited tumor growth and suppressed cell autophagy in vivo. Moreover, LCPAT1 knockdown in lung cancer cell lines resulted in decreased autophagy-associated gene expression and alleviated the cell autophagy induced by rapamycin. Conclusions:We speculate that LCPAT1 plays a crucial role in regulating autophagy in lung cancer.

show abstract

“…Furthermore, the yeast atg8 orthologs of the LC3/GABARAP protein family fulfill specialized roles in the execution of autophagy (2). This family consists of seven active members [LC3A (two splicing variants; LC3A-a and LC3A-b), LC3B, LC3C, GABARAP, GABARAPL1, and GABARAPL2], which share a high mutual homology, including a conserved C-terminal glycine residue for phosphatidylethanolamine (PE) conjugation to allow membrane association.…”

Section: Autophagymentioning

confidence: 99%

“…Despite the high grade of homology, the protein family members harbor individual roles in autophagy and are associated with autophagy unrelated functions, such as receptor trafficking, too (2). …”

Section: Autophagymentioning

confidence: 99%

Autophagy-Dependent Secretion: Contribution to Tumor Progression

2016

Self Cite

View full text Add to dashboard Cite

Autophagy is best known as a lysosomal degradation and recycling pathway to maintain cellular homeostasis. During autophagy, cytoplasmic content is recognized and packed in autophagic vacuoles, or autophagosomes, and targeted for degradation. However, during the last years, it has become evident that the role of autophagy is not restricted to degradation alone but also mediates unconventional forms of secretion. Furthermore, cells with defects in autophagy apparently are able to reroute their cargo, like mitochondria, to the extracellular environment; effects that contribute to an array of pathologies. In this review, we discuss the current knowledge of the physiological roles of autophagy-dependent secretion, i.e., the effect on inflammation and insulin/hormone secretion. Finally, we focus on the effects of autophagy-dependent secretion on the tumor microenvironment (TME) and tumor progression. The autophagy-mediated secreted factors may stimulate cellular proliferation via auto- and paracrine signaling. The autophagy-mediated release of immune modulating proteins changes the immunosuppresive TME and may promote an invasive phenotype. These effects may be either direct or indirect through facilitating formation of the mobilized vesicle, aid in anterograde trafficking, or alterations in homeostasis and/or autonomous cell signaling.

show abstract

LC3/GABARAP family proteins: autophagy‐(un)related functions

Cited by 509 publications

References 133 publications

Artesunate Attenuates Pro-Inflammatory Cytokine Release from Macrophages by Inhibiting TLR4-Mediated Autophagic Activation via the TRAF6-Beclin1-PI3KC3 Pathway

Artesunate Attenuates Pro-Inflammatory Cytokine Release from Macrophages by Inhibiting TLR4-Mediated Autophagic Activation via the TRAF6-Beclin1-PI3KC3 Pathway

Knockdown of long non-coding RNA LCPAT1 inhibits autophagy in lung cancer

Autophagy-Dependent Secretion: Contribution to Tumor Progression

Contact Info

Product

Resources

About