Редактирование: ATG5

Autophagy protein 5 (APG5-like) (Apoptosis-specific protein) [APG5L] [ASP]

==Publications==

{{medline-entry
|title=Autophagy and heat-shock response impair stress granule assembly during cellular senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33049246
|abstract=Stress granules (SGs) are membraneless organelles formed in response to insult. These granules are related to pathological granules found in age-related neurogenerative diseases such as Parkinson's and Alzheimer's. Previously, we demonstrated that senescent cells, which accumulate with age, exposed to chronic oxidative stress, are unable to form SGs. Here, we show that the senescent cells' inability to form SGs correlates with an upregulation in both the heat-shock response and autophagy pathways, both of which are well-established promoters of SG disassembly. Our data also reveals that the knockdown of HSP70 and [[ATG5]], important components of the heat-shock response and autophagy pathways, respectively, restores the number of SGs formed in senescent cells exposed to chronic oxidative stress. Surprisingly, under these conditions, the depletion of HSP70 or [[ATG5]] did not affect the clearance of these SGs during their recovery from chronic stress. These data reveal that senescent cells possess a unique heat-shock and autophagy-dependent ability to impair the formation of SGs in response to chronic stress, thereby expanding the existing understanding of SG dynamics in senescent cells and their potential contribution to age-related neurodegenerative diseases.

|keywords=* Ageing
* Cellular senescence
* Molecular biology
* Oxidative stress
* Stress granules
|full-text-url=https://sci-hub.do/10.1016/j.mad.2020.111382
}}
{{medline-entry
|title=Effects of [[MUL1]] and PARKIN on the circadian clock, brain and behaviour in Drosophila Parkinson's disease models.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31138137
|abstract=Mutants which carry mutations in genes encoding mitochondrial ligases [[MUL1]] and PARKIN are convenient Drosophila models of Parkinson's disease (PD). In several studies it has been shown that in Parkinson's disease sleep disturbance occurs, which may be the result of a disturbed circadian clock. We found that the ROS level was higher, while the anti-oxidant enzyme [[SOD1]] level was lower in mul1  and park  mutants than in the white mutant used as a control. Moreover, mutations of both ligases affected circadian rhythms and the clock. The expression of clock genes per, tim and clock and the level of PER protein were changed in the mutants. Moreover, expression of [[ATG5]], an autophagy protein also involved in circadian rhythm regulation, was decreased in the brain and in [[PDF]]-immunoreactive large ventral lateral clock neurons. The observed changes in the molecular clock resulted in a longer period of locomotor activity rhythm, increased total activity and shorter sleep at night. Finally, the lack of both ligases led to decreased longevity and climbing ability of the flies. All of the changes observed in the brains of these Drosophila models of PD, in which mitochondrial ligases [[MUL1]] and PARKIN do not function, may explain the mechanisms of some neurological and behavioural symptoms of PD.
|mesh-terms=* Animals
* Animals, Genetically Modified
* Brain
* CLOCK Proteins
* Circadian Clocks
* Circadian Rhythm
* Disease Models, Animal
* Drosophila
* Drosophila Proteins
* Locomotion
* Longevity
* Motor Skills
* Mutation
* Neurons
* Parkinson Disease
* Reactive Oxygen Species
* Sleep
* Superoxide Dismutase
* Ubiquitin-Protein Ligases
|keywords=* Autophagy
* Clock genes
* Clock neurons
* Locomotor activity rhythm
* Mitochondrial ligases
* ROS
* SOD1
* Sleep
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540415
}}
{{medline-entry
|title=Lifelong Football Training: Effects on Autophagy and Healthy Longevity Promotion.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30837897
|abstract=Aging is a physiological process characterized by a progressive decline of biological functions and an increase in destructive processes in cells and organs. Physical activity and exercise positively affects the expression of skeletal muscle markers involved in longevity pathways. Recently, a new mechanism, autophagy, was introduced to the adaptations induced by acute and chronic exercise as responsible of positive metabolic modification and health-longevity promotion. However, the molecular mechanisms regulating autophagy in response to physical activity and exercise are sparsely described. We investigated the long-term adaptations resulting from lifelong recreational football training on the expression of skeletal muscle markers involved in autophagy signaling. We demonstrated that lifelong football training increased the expression of messengers: [[RAD23A]], [[HSPB6]], [[RAB1B]], [[TRAP1]], [[SIRT2]], and HSBPB1, involved in the auto-lysosomal and proteasome-mediated protein degradation machinery; of RPL1, [[RPL4]], [[RPL36]], MRLP37, involved in cellular growth and differentiation processes; of the Bcl-2, HSP70, HSP90, [[PSMD13]], and of the [[ATG5]]-[[ATG12]] protein complex, involved in proteasome promotion and autophagy processes in muscle samples from lifelong trained subjects compared to age-matched untrained controls. In conclusion, our results indicated that lifelong football training positively influence exercise-induced autophagy processes and protein quality control in skeletal muscle, thus promoting healthy aging.

|keywords=* autophagy
* cardiovascular capacity
* football
* lifelong training
* longevity
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390296
}}
{{medline-entry
|title=The [[ATG5]]-binding and coiled coil domains of [[ATG16L1]] maintain autophagy and tissue homeostasis in mice independently of the WD domain required for LC3-associated phagocytosis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30403914
|abstract=Macroautophagy/autophagy delivers damaged proteins and organelles to lysosomes for degradation, and plays important roles in maintaining tissue homeostasis by reducing tissue damage. The translocation of LC3 to the limiting membrane of the phagophore, the precursor to the autophagosome, during autophagy provides a binding site for autophagy cargoes, and facilitates fusion with lysosomes. An autophagy-related pathway called LC3-associated phagocytosis (LAP) targets LC3 to phagosome and endosome membranes during uptake of bacterial and fungal pathogens, and targets LC3 to swollen endosomes containing particulate material or apoptotic cells. We have investigated the roles played by autophagy and LAP in vivo by exploiting the observation that the WD domain of [[ATG16L1]] is required for LAP, but not autophagy. Mice lacking the linker and WD domains, activate autophagy, but are deficient in LAP. The LAP  mice survive postnatal starvation, grow at the same rate as littermate controls, and are fertile. The liver, kidney, brain and muscle of these mice maintain levels of autophagy cargoes such as LC3 and [[SQSTM1]]/p62 similar to littermate controls, and prevent accumulation of [[SQSTM1]] inclusions and tissue damage associated with loss of autophagy. The results suggest that autophagy maintains tissue homeostasis in mice independently of LC3-associated phagocytosis. Further deletion of glutamate E230 in the coiled-coil domain required for [[WIPI2]] binding produced mice with defective autophagy that survived neonatal starvation. Analysis of brain lysates suggested that interactions between [[WIPI2]] and [[ATG16L1]] were less critical for autophagy in the brain, which may allow a low level of autophagy to overcome neonatal lethality. Abbreviations: CCD: coiled-coil domain; CYBB/NOX2: cytochrome b-245: beta polypeptide; GPT/ALT: glutamic pyruvic transaminase: soluble; LAP: LC3-associated phagocytosis; LC3: microtubule-associated protein 1 light chain 3; MEF: mouse embryonic fibroblast; NOD: nucleotide-binding oligomerization domain; NADPH: nicotinamide adenine dinucleotide phosphate; RUBCN/Rubicon: RUN domain and cysteine-rich domain containing Beclin 1-interacting protein; SLE: systemic lupus erythematosus; [[SQSTM1]]/p62: sequestosome 1; TLR: toll-like receptor; TMEM: transmembrane protein; TRIM: tripartite motif-containing protein; UVRAG: UV radiation resistance associated gene; WD: tryptophan-aspartic acid; WIPI: WD 40 repeat domain: phosphoinositide interacting.
|mesh-terms=* Animals
* Autophagy
* Autophagy-Related Protein 5
* Autophagy-Related Proteins
* Brain
* Carrier Proteins
* Cytokines
* Female
* Fibroblasts
* Homeostasis
* Kidney
* Liver
* Longevity
* Macrophages
* Male
* Mice
* Mice, Inbred C57BL
* Mice, Transgenic
* Microtubule-Associated Proteins
* Muscles
* Phagocytosis
* Phagosomes
* WD40 Repeats
|keywords=* ATG16L1
* LC3-associated phagocytosis
* WD domain
* WIPI2
* brain
* sequestosome 1/p62 inclusions
* tissue homeostasis
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526875
}}
{{medline-entry
|title=Inhibition of glioma growth by flavokawain B is mediated through endoplasmic reticulum stress induced autophagy.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30025493
|abstract=Flavokawain B (FKB), a natural kava chalcone, displays potent antitumor activity in various types of cancer. The mechanism of action, however, remains unclear. Here, we evaluated the efficacy of FKB in the treatment of human glioblastoma multiforme (GBM) as well as the molecular basis for its inhibitory effects in cancer. Approximately 60% of GBM cells became senescent after treatment with FKB as assessed in the senescence-associated (SA)-GLB1/SA-β-galactosidase assay. The cellular process of autophagy potentially contributed to the establishment of senescence. Transmission electron microscopy revealed the formation of autophagic vesicles under FKB treatment, and [[MAP1LC3B]] (microtubule associated protein 1 light chain 3 beta)-II was increased. Transfection of [[ATG5]] or [[ATG7]] small interfering RNAs (siRNAs) inhibited FKB-induced autophagy in U251 cells. Western blot revealed that molecular components of the endoplasmic reticulum stress pathway were activated, including [[ATF4]] (activating transcription factor 4) and [[[[DDIT3]]]] (DNA damage inducible transcript 3), while levels of [[TRIB3]] (tribbles pseudokinase 3) increased. In addition, based on the phosphorylation status, the AKT-[[MTOR]]-[[RPS6KB1]] pathway was inhibited, which induced autophagy in GBM cells. Inhibition of autophagy by autophagy inhibitors 3-methyladenine and chloroquine or knockdown of [[ATG5]] or [[ATG7]] caused FKB-treated U251 cells to switch from senescence to apoptosis. Finally, knockdown of [[ATG5]] or treatment with chloroquine in combination with FKB, significantly inhibited tumor growth in vivo. Our results demonstrated that FKB induced protective autophagy through the [[ATF4]]-[[[[DDIT3]]]]-[[TRIB3]]-AKT-[[MTOR]]-[[RPS6KB1]] signaling pathway in GBM cells, indicating that the combination treatment of FKB with autophagy inhibitors may potentially be an effective therapeutic strategy for GBM. 3-MA: 3-methyladenine; 4-PBA: 4-phenylbutyrate; AKT: AKT serine/threonine kinase; [[ATF4]]: activating transcription factor 4; ATG: autophagy related; CASP3: caspase 3; [[CCK]]-8: cell counting kit-8; CDKN1A: cyclin-dependent kinase inhibitor 1A; CQ: chloroquine; [[[[DDIT3]]]]: DNA damage inducible transcript 3; DMEM: Dulbecco's modified Eagle's medium; EIF2A: eukaryotic translation initiation factor 2A; EIF2AK3: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; FKB: flavokawain B; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GBM: glioblastoma multiforme; GFP: green fluorescent protein; HSPA5: heat shock protein family A (Hsp70) member 5; [[MAP1LC3B]]: microtubule associated protein 1 light chain 3 beta; [[MTOR]]: mechanistic target of rapamycin kinase; PARP1: poly(ADP-ribose) polymerase; 1[[RPS6KB1]]: ribosomal protein S6 kinase B1; SA-GLB1: senescence-associated galactosidase beta 1; siRNA: short interfering RNA; SQSTM1: sequestosome 1; TEM: transmission electron microscopy; [[TRIB3]]: tribbles pseudokinase 3; TUNEL: deoxynucleotidyl transferase-mediated dUTP nick-end labeling.
|mesh-terms=* Animals
* Antineoplastic Agents, Phytogenic
* Autophagy
* Autophagy-Related Protein 5
* Autophagy-Related Protein 7
* Cell Proliferation
* Cells, Cultured
* Endoplasmic Reticulum Stress
* Flavonoids
* Gene Expression Regulation, Neoplastic
* Glioma
* Humans
* Male
* Mice
* Mice, Nude
* Xenograft Model Antitumor Assays
|keywords=* Apoptosis
* ER stress
* autophagy
* flavokawain B
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152528
}}
{{medline-entry
|title=Carvacrol nanoemulsion evokes cell cycle arrest, apoptosis induction and autophagy inhibition in doxorubicin resistant-A549 cell line.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29405784
|abstract=Carvacrol is a monoterpenoid flavonoid found abundantly in thyme plants. Its physiochemical instability and partial solubility in water is the principal limitation for its industrial use. Hence, we made a carvacrol nanoemulsion (CANE) using ultrasonication method and characterized it by dynamic light scattering (DLS) technique which revealed a negative surface charge (-29.89 mV) with 99.1 nm average droplet size. CANE effectively induced apoptosis in doxorubicin-resistant A549 lung carcinoma cells (A549 ) evident by the elevated expression of apoptotic proteins such as Bax, Cytochrome C, and Cleaved caspase 3 and 9. Also, CANE displayed cell senescence leading to cell cycle arrest by reducing [[CDK2]], [[CDK4]], [[CDK6]], Cyclin E, Cyclin D1 and enhancing p21 protein expression. In addition, a potential role of CANE in the inhibition of autophagy was noted by evaluating the reduced conversion of LC-3 I to II. Beside this, a down-regulation of important autophagy markers [[ATG5]] and [[ATG7]] and upregulation of p62 were detected in response to CANE. We conclude that the synthesized CANE has potential to cause cell senescence, cell cycle arrest, autophagy inhibition and apoptosis in A549  cells and could be used as a potential candidate for lung cancer therapy.
|mesh-terms=* A549 Cells
* Animals
* Apoptosis
* Autophagy
* Cell Cycle Checkpoints
* Cellular Senescence
* Cymenes
* Dose-Response Relationship, Drug
* Doxorubicin
* Drug Resistance, Neoplasm
* Emulsions
* Humans
* Mice
* Mitochondria
* Monoterpenes
* Nanostructures
* Oxidative Stress
* Xenograft Model Antitumor Assays
|keywords=* Carvacrol nanoemulsion
* apoptosis
* autophagy
* cell senescence
|full-text-url=https://sci-hub.do/10.1080/21691401.2018.1434187
}}
{{medline-entry
|title=Compromised autophagy precedes meniscus degeneration and cartilage damage in mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28801209
|abstract=Autophagy is a cellular homeostasis mechanism that facilitates normal cell function and survival. Objectives of this study were to determine associations between autophagic responses with meniscus injury, joint aging, and osteoarthritis (OA), and to establish the temporal relationship with structural changes in menisci and cartilage. Constitutive activation of autophagy during aging was measured in GFP-LC3 transgenic reporter mice between 6 and 30 months. Meniscus injury was created by surgically destabilizing the medial meniscus (DMM) to induce posttraumatic OA in C57BL/6J mice. Levels of autophagy proteins and activation were analyzed by confocal microscopy and immunohistochemistry. Associated histopathological changes, such as cellularity, matrix staining, and structural damage, were graded in the meniscus and compared to changes in articular cartilage. In C57BL/6J mice, basal autophagy was lower in the meniscus than in articular cartilage. With increasing age, expression of the autophagy proteins [[ATG5]] and LC3 was significantly reduced by 24 months. Age-related changes included abnormal Safranin-O staining and reduced cellularity, which preceded structural damage in the meniscus and articular cartilage. In mice with DMM, autophagy was induced in the meniscus while it was suppressed in cartilage. Articular cartilage exhibited the most profound changes in autophagy and structure that preceded meniscus degeneration. Systemic administration of rapamycin to mice with DMM induced autophagy activation in cartilage and reduced degenerative changes in both meniscus and cartilage. Autophagy is significantly affected in the meniscus during aging and injury and precedes structural damage. Maintenance of autophagic activity appears critical for meniscus and cartilage integrity.
|mesh-terms=* Aging
* Animals
* Autophagy
* Autophagy-Related Protein 5
* Cartilage, Articular
* Green Fluorescent Proteins
* Immunosuppressive Agents
* Menisci, Tibial
* Mice
* Mice, Inbred C57BL
* Mice, Transgenic
* Microscopy, Confocal
* Microtubule-Associated Proteins
* Osteoarthritis, Knee
* Sirolimus
* Tibial Meniscus Injuries
|keywords=* Aging
* Autophagy
* Cartilage
* Meniscus
* Osteoarthritis
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650923
}}
{{medline-entry
|title=Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28238968
|abstract=Aging causes a general decline in cellular metabolic activity, and function in different tissues and whole body homeostasis. However, the understanding about the metabolomic and autophagy changes in skeletal muscle and heart during aging is still limited. We thus examined markers for macroautophagy, chaperone-mediated autophagy (CMA), mitochondrial quality control, as well as cellular metabolites in skeletal and cardiac muscle from young (5 months old) and aged (27 months old) mice. We found decreased autophagic degradation of p62 and increased ubiquitinated proteins in both tissues from aged mice, suggesting a decline in macroautophagy during aging. In skeletal muscle from aged mice, there also was a decline in LC3B-I conjugation to phosphatidylethanolamine (PE) possibly due to decreased protein levels of [[ATG3]] and [[ATG12]]-[[ATG5]]. The CMA markers, LAMP-2A and Hsc70, and mitochondrial turnover markers, Drp1, [[PINK1]] and PGC1α also were decreased. Metabolomics analysis showed impaired β-oxidation in heart of aged mice, whereas increased branched-chain amino acids (BCAAs) and ceramide levels were found in skeletal muscle of aged mice that in turn, may contribute to insulin resistance in muscle. Taken together, our studies showed similar declines in macroautophagy but distinct effects on CMA, mitochondrial turnover, and metabolic dysfunction in muscle [i]vs.[/i] heart during aging.
|mesh-terms=* Aging
* Animals
* Autophagy
* Biomarkers
* Energy Metabolism
* Lysosomes
* Mice
* Mitochondria
* Molecular Chaperones
* Muscle, Skeletal
* Myocardium
|keywords=* aging
* autophagy
* ceramide
* chaperone-mediated autophagy (CMA)
* fatty acid oxidation
* heart
* muscle
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5361683
}}
{{medline-entry
|title=Macroautophagy is impaired in old murine brain tissue as well as in senescent human fibroblasts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27825071
|abstract=The overall decrease in proteolytic activity in aging can promote and accelerate protein accumulation and metabolic disturbances. To specifically analyze changes in macroautophagy (MA) we quantified different autophagy-related proteins (ATGs) in young, adult and old murine tissue as well as in young and senescent human fibroblasts. Thus, we revealed significantly reduced levels of [[ATG5]]-[[ATG12]], LC3-II/LC3-I ratio, Beclin-1 and p62 in old brain tissue and senescent human fibroblasts. To investigate the role of mTOR, the protein itself and its target proteins p70S6 kinase and 4E-BP1 were quantified. Significant increased mTOR protein levels were determined in old tissue and cells. Determination of phosphorylated and basal amount of both proteins suggested higher mTOR activity in old murine tissue and senescent human fibroblasts. Besides the reduced levels of ATGs, mTOR can additionally reduce MA, promoting further acceleration of protein accumulation and metabolic disturbances during aging.
|mesh-terms=* Adaptor Proteins, Signal Transducing
* Aging
* Animals
* Autophagy
* Autophagy-Related Proteins
* Brain
* Carrier Proteins
* Cell Cycle Proteins
* Cellular Senescence
* Down-Regulation
* Eukaryotic Initiation Factors
* Fibroblasts
* Gene Expression Regulation, Developmental
* Humans
* Male
* Mice
* Phosphoproteins
* Phosphorylation
* Ribosomal Protein S6 Kinases, 70-kDa
* TOR Serine-Threonine Kinases
|keywords=* ATGs
* Aging
* Autophagy-lysosome pathway
* Fibroblasts
* MTOR
* Senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099282
}}
{{medline-entry
|title=[[ATG5]]-knockout mutants of Physcomitrella provide a platform for analyzing the involvement of autophagy in senescence processes in plant cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26368055
|abstract=Autophagy is a pathway in which a cell degrades part of its cytoplasm in vacuoles or lysosomes. To identify the physiological functions of autophagy in plants, we disrupted [[ATG5]], an autophagy-related gene, in Physcomitrella, and confirmed that atg5 mutants are deficient in the process of autophagy. On carbon or nitrogen starvation medium, atg5 colonies turned yellow earlier than the wild-type (WT) colonies, showing that Physcomitrella atg5 mutants, like yeast and Arabidopsis, are sensitive to nutrient starvation. In the dark, even under nutrient-sufficient conditions, colonies turned yellow and the net degradation of chlorophyll and Rubisco protein occurred together with the upregulation of several senescence-associated genes. Yellowing reactions were inhibited by the protein synthesis inhibitor cycloheximide, suggesting that protonemal colonies undergo dark-induced senescence like the green leaves of higher plants. Such senescence responses in the dark occurred earlier in atg5 colonies than WT colonies. The sugar content was almost the same between WT and atg5 colonies, indicating that the early-senescence phenotype of atg5 is not explained by sugar deficiency. However, the levels of 7 amino acids showed significantly different alteration between atg5 and WT in the dark: 6 amino acids, particularly arginine and alanine, were much more deficient in the atg5 mutants, irrespective of the early degradation of Rubisco protein. On nutrient-sufficient medium supplemented with casamino acids, the early-senescence phenotype was slightly moderated. We propose that the early-senescence phenotype in atg5 mutants is partly explained by amino acid imbalance because of the lack of cytoplasmic degradation by autophagy in Physcomitrella.
|mesh-terms=* Amino Acids
* Autophagy
* Bryopsida
* Carbohydrates
* Cellular Senescence
* Chlorophyll
* Culture Media
* Cycloheximide
* Darkness
* Gene Expression Regulation, Plant
* Gene Knockout Techniques
* Genes, Plant
* Mutation
* Phenotype
* Plant Cells
* Plant Proteins
* Ribulose-Bisphosphate Carboxylase
* Solubility
|keywords=* Physcomitrella
* amino acid
* autophagy
* bryophyte
* senescence
* sugar
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4883962
}}
{{medline-entry
|title=Differential regulation of autophagy and cell viability by ceramide species.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25803131
|abstract=The present studies sought to determine whether the anti-folate pemetrexed (Alimta) and the sphingosine-1-phosphate receptor modulator FTY720 (Fingolimod, Gilenya) interacted to kill tumor cells. FTY720 and pemetrexed interacted in a greater than additive fashion to kill breast, brain and colorectal cancer cells. Loss of p53 function weakly enhanced the toxicity of FTY720 whereas deletion of activated RAS strongly or expression of catalytically inactive AKT facilitated killing. Combined drug exposure reduced the activity of AKT, p70 S6K and mTOR and activated JNK and p38 MAPK. Expression of activated forms of AKT, p70 S6K and mTOR or inhibition of JNK and p38 MAPK suppressed the interaction between FTY720 and pemetrexed. Treatment of cells with FTY720 and pemetrexed increased the numbers of early autophagosomes but not autolysosomes, which correlated with increased LC3II processing and increased p62 levels, suggestive of stalled autophagic flux. Knock down of [[ATG5]] or Beclin1 suppressed autophagosome formation and cell killing. Knock down of ceramide synthase 6 suppressed autophagosome production and cell killing whereas knock down of ceramide synthase 2 enhanced vesicle formation and facilitated death. Collectively our findings argue that pemetrexed and FTY720 could be a novel adjunct modality for breast cancer treatment. 
|mesh-terms=* Autophagy
* Cell Line, Tumor
* Cell Survival
* Ceramides
* Fingolimod Hydrochloride
* Humans
* Pemetrexed
* Signal Transduction
|keywords=* Ad, adenovirus
* Alimta
* CMV, empty vector plasmid or virus
* CerS, ceramide synthase
* CerS2
* CerS6
* ER, endoplasmic reticulum
* ERK, extracellular regulated kinase
* FTY720
* Gilenya
* IP, immunoprecipitation
* LASS, longevity assurance gene
* MAPK, mitogen activated protein kinase
* MEK, mitogen activated extracellular regulated kinase
* PI3K, phosphatidyl inositol 3 kinase
* PTEN, phosphatase and tensin homolog on chromosome 10
* PTX, pemetrexed
* Pemetrexed
* ROS, reactive oxygen species
* S1P
* SCR, scrambled
* VEH, vehicle.
* autophagy
* ca, constitutively active
* ceramide
* dn, dominant negative
* mTOR, mammalian target of rapamycin
* si, small interfering
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623104
}}
{{medline-entry
|title=Autophagy suppresses melanoma tumorigenesis by inducing senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24300435
|abstract=Whether and how autophagy is involved in tumorigenesis is poorly understood. We approached this question by investigating a relatively large cohort of patients with mostly early primary melanoma for their expression of 2 markers for autophagy, the protein [[ATG5]] (autophagy-related 5) and MAP1LC3B/LC3 (microtubule-associated protein 1 light chain 3B). Surprisingly, we discovered that both [[ATG5]] and LC3 levels are decreased in patients with melanomas as compared with those with benign nevi. We wondered why reduced autophagy should facilitate early tumor development. Using an in vitro model of melanoma tumorigenesis, in which a mutated oncogene, [[BRAF]] (v-raf murine sarcoma viral oncogene homolog B), had been introduced into normal human melanocytes, we were able to show that downregulation of [[ATG5]] promoted the proliferation of melanocytes because it facilitated bypassing oncogene-induced senescence (OIS). Our work supports previous reports that had argued that autophagy actually suppresses tumorigenesis and explains the possible mechanism. Furthermore, our findings suggest that the status of [[ATG5]] and autophagy could serve as a diagnostic marker for distinguishing benign from malignant tumors of melanocytes. 
|mesh-terms=* Autophagy
* Autophagy-Related Protein 5
* Carcinogenesis
* Cell Line, Tumor
* Cell Proliferation
* Cell Transformation, Neoplastic
* Cellular Senescence
* Humans
* Melanoma
* Microtubule-Associated Proteins
|keywords=* ATG5
* autophagy
* epigenetics
* melanoma
* promoter methylation
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5396100
}}
{{medline-entry
|title=Deletion of [[ATG5]] shows a role of autophagy in salivary homeostatic control.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23884556
|abstract=Autophagy is a catabolic pathway utilized to maintain a balance among the synthesis, degradation, and recycling of cellular components, thereby playing a role in cell growth, development, and homeostasis. Previous studies revealed that a conditional knockout of essential member(s) of autophagy in a variety of tissues causes changes in structure and function of these tissues. Acinar cell-specific expression of knocked-in Cre recombinase through control of aquaporin 5 (Aqp5) promoter/enhancer (Aqp5-Cre) allows us to specifically inactivate Atg5, a protein necessary for autophagy, in salivary acinar cells of Atg5(f/f);Aqp5-Cre mice. There was no difference in apoptotic or proliferation levels in salivary glands of Atg5/Cre mice from each genotype. However, H