MIR181Aregulates starvation- and rapamycin-induced autophagy through targeting ofATG5

Tekirdağ, Kumsal Ayşe; Korkmaz, Gözde; Öztürk, Deniz Gülfem; Agami, Reuven; Gözüaçık, Devrim

doi:10.4161/auto.23117

Cited by 151 publications

(122 citation statements)

References 59 publications

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“…As expected, overexpression of ATG5 resulted in an increased ATG12-ATG5 conjugation and therefore enhanced the basal autophagy levels (Fig. 4A), which is consistent with other recent reports (34,39). The BafA1 flux assay further demonstrated that ATG5 overexpression increased the autophagosome formation rather than decreased the autophagosome maturation (Fig.…”

Section: Atg12-atg5 Interacts With Cav-1 In Cytosolsupporting

confidence: 80%

“…However, recently it has been reported that in MCF-7 cells overexpression of ATG5 could rescue the autophagic activity (39), and overexpression of ATG5 in mice could activate autophagy and extend lifespan in vivo (34). Thus the effects of overexpression of these ATG proteins in regulation of autophagy may vary between different cells and study models.…”

Section: Discussionmentioning

confidence: 99%

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Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung epithelial cells

Chen

Cao

Zhou

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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AM, Shen H. Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 306: L1016 -L1025, 2014. First published April 11, 2014 doi:10.1152/ajplung.00268.2013.-Autophagy plays a pivotal role in cellular homeostasis and adaptation to adverse environments, although the regulation of this process remains incompletely understood. We have recently observed that caveolin-1 (Cav-1), a major constituent of lipid rafts on plasma membrane, can regulate autophagy in cigarette smoking-induced injury of lung epithelium, although the underlying molecular mechanisms remain incompletely understood. In the present study we found that Cav-1 interacted with and regulated the expression of ATG12-ATG5, an ubiquitin-like conjugation system crucial for autophagosome formation, in lung epithelial Beas-2B cells. Deletion of Cav-1 increased basal and starvation-induced levels of ATG12-ATG5 and autophagy. Biochemical analyses revealed that Cav-1 interacted with ATG5, ATG12, and their active complex ATG12-ATG5. Overexpression of ATG5 or ATG12 increased their interactions with Cav-1, the formation of ATG12-ATG5 conjugate, and the subsequent basal levels of autophagy but resulted in decreased interactions between Cav-1 and another molecule. Knockdown of ATG12 enhanced the ATG5-Cav-1 interaction. Mutation of the Cav-1 binding motif on ATG12 disrupted their interaction and further augmented autophagy. Cav-1 also regulated the expression of ATG16L, another autophagy protein associating with the ATG12-ATG5 conjugate during autophagosome formation. Altogether these studies clearly demonstrate that Cav-1 competitively interacts with the ATG12-ATG5 system to suppress the formation and function of the latter in lung epithelial cells, thereby providing new insights into the molecular mechanisms by which Cav-1 regulates autophagy and suggesting the important function of Cav-1 in certain lung diseases via regulation of autophagy homeostasis.caveolin-1; ATG12-ATG5; ATG16L; autophagy; lung diseases AUTOPHAGY IS A DYNAMIC PROCESS responsible for the turnover of cellular organelles and long-lived proteins. During this process, cytosolic proteins and organelles (e.g., mitochondria and endoplasmic reticulum) are engulfed into double-membranebound vesicles, autophagosomes. The outer membrane of the autophagosome subsequently fuses with lysosomes to form autolysosomes in which the engulfed components are degraded by lysosomal hydrolases, regenerating metabolic precursors that are recycled for macromolecular synthesis and ATP generation (20, 42). Autophagy is induced above basal levels in response to diverse stimuli including nutrient starvation, genotoxic agents, cytokines, and oxidative stress. This process provides an essential function in the maintenance of cellular homeostasis and adaptation to adverse environments (16,29,35).More than 30 autophagy-related genes and gene products critical in the regulation of autophagy, designated "ATG," have been identified heretofore in yeast and hi...

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Section: Atg12-atg5 Interacts With Cav-1 In Cytosolsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung epithelial cells

Chen

Cao

Zhou

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Several miRNAs have played a vital role in endothelial cell pathophysiology, such as cellular senescence, angiogenesis, and vascular inflammation (48). Some miRNAs can either activate or inhibit in the process of autophagy and hence, influence the cells' functions (48,49,56). In a previous experiment, Li et al (26) found that highglucose-induced suppression of migration might be associated with miR-221 in HUVECs.…”

Section: Discussionmentioning

confidence: 99%

miR-1273g-3p participates in acute glucose fluctuation-induced autophagy, dysfunction, and proliferation attenuation in human umbilical vein endothelial cells

Guo

Sang

Yin

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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-Acute glucose fluctuations (AGF) often cause high mortality among critically ill patients, but the mechanisms induced by AGF are not clear. Recent studies suggest that endothelial dysfunction is a key factor that leads to high mortality among critically ill patients. Our goal is to evaluate the phenomenon and mechanisms of endothelial dysfunction induced by AGF. In this study, the functions of human umbilical vein endothelial cells (HUVECs) were compared after treatment with sustained high glucose (SHG), AGF in two groups (AGF1 fluctuations between 5 and 16 mM and AGF2 fluctuations between 5 and 25 mM), and normal glucose levels as a control group (CTR). The medium of the groups was changed every 4 h. The influence of AGF on wound healing was also tested on C57BL/6 mice. The results show that cell proliferation, angiogenesis, and migration functions were injured in the SHG and both AGF groups. AGF2 group shows the worse condition in vitro. In vivo, the wound healing was delayed after the AGF treatment. Furthermore, the markers of apoptosis and autophagy were analyzed. We observed that the autophagy changed in all treatment groups, but apoptosis showed no change. To get to know the mechanism of dysfunction and autophagy, we performed the microRNA chip assay and real-time PCR and found miR-1273g-3p remarkably changed in AGF2 group. After the mimic and inhibitor of miR-1273g-3p were transfected during the AGF2 treatment, we found that the dysfunction and autophagy were partially enhanced by miR-1273g-3p mimic and reversed by miR-1273g-3p inhibitor in AGF2 group. Thus, we conclude that AGF can induce more dysfunction and autophagy, and miR-1273g-3p is also an important factor that leads to the injury. glucose fluctuations; endothelial dysfunction; wound healing; autophagy; miR-1273g-3pINCREASING GLYCEMIC VARIABILITY can greatly increase the risk of mortality among critically ill patients. Several previous studies suggest that the variability in glucose levels over time is an important determinant of mortality among critically ill patients (21,22,58). Alternatively, recent evidence shows that glucose fluctuations may influence the development of diabetic complications(4, 47) and may produce more serious injury in organ functions than sustained high blood glucose. Krinsley and Preiser (20) reported that if a blood glucose range of 70 -140 mg/dl is maintained for Ͼ80% of the time, the chances of survival of nondiabetic critically ill adults will be greatly increased. Organ injury induced by glucose toxicity is commonly observed in both intensive care units and endocrine departments. The damage is also observed in in vitro cell culture and animal studies. Therefore, some authors have proposed that "glycemic variability" is a new therapeutic challenge in diabetes and the critical care setting (7).The mechanism of the production of glucose fluctuations is variable in several studies (35)(36)(37)(38)(39)57) in both preclinical and clinical research studies. However, this is not appropriate for the critically ill patient...

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“…p62/SQSTM1 fluorescence was quantified and expressed as a percentage of vehicle control; each data point represents the mean of a minimum of three independent experiments, with error bars representing the standard error of the mean (SEM). 3-methyladenine and rapamycin (Sigma-Aldrich) were used as inhibitors and activators of autophagy, respectively [26][27][28].…”

Section: 6! Autophagy Analysismentioning

confidence: 99%

Activation of the Farnesoid X-receptor in breast cancer cell lines results in cytotoxicity but not increased migration potential

et al. 2016

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MIR181Aregulates starvation- and rapamycin-induced autophagy through targeting ofATG5

Cited by 151 publications

References 59 publications

Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung epithelial cells

Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung epithelial cells

miR-1273g-3p participates in acute glucose fluctuation-induced autophagy, dysfunction, and proliferation attenuation in human umbilical vein endothelial cells

Activation of the Farnesoid X-receptor in breast cancer cell lines results in cytotoxicity but not increased migration potential

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