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Showing 1 to 20 of 22 for “"ULK1"”.
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Investigating the role of ULK1 kinase activity during autophagy
… to be regulated by the serine/threonine kinases ULK1/2. ULK1/2 kinase activity is required for amino acid starvation-induced and other types of autophagy. Our lab recently showed that inhibition of ULK1 with the potent compound MRT68921, results in formation of stalled autophagosomes that are …
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Dissecting the Physiological Roles of ULK1/2 in the Mouse Brain
<p>Mammalian UNC-51–like kinases 1 and 2 (ULK1 and ULK2), Caenorhabditis elegans UNC-51 and Drosophila melanogaster Atg1 are redundant serine/threonine kinases that regulate flux through the autophagy pathway in response to various types of cellular stress. C. elegans UNC-51 and D. melanogaster …
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Impaired Ulk1 Ser555 Phosphorylation Promotes Amino Acid Reliance and Links Mitochondrial Inefficiency to Systemic Metabolic Inflexibility
… Unc-51-like autophagy activating kinase 1 (Ulk1) is a serine/threonine kinase best known for initiating autophagy, but also serves as a nutrient-sensing hub regulated by AMPK and mTORC1. AMPK activates Ulk1 via phosphorylation at serine 555 (S555) during energetic stress, while mTORC1 …
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Xenophagy in response to gram-positive staphylococcus aureus and gram-negative salmonella enterica sv. typhimurium
… autophagosomes, leading to eventual cell death. ULK1 is a serine/threonine kinase that plays an essential role during the early steps of autophagosome biogenesis, but its roles during xenophagy following Staphylococcus aureus infection have been unclear. ULK1 represents an excellent candidate for …
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A study on non-canonical autophagy signalling
… activates multiple downstream regulators such as ULK1, which in the canonical pathway is known to activate the VPS34 complex, resulting in the formation of PI(3)P-containing autophagosomes. A failure to induce functional autophagy has been implicated in a range of neurodegenerative diseases, in …
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Differential regulation of the phosphorylated and dephosphorylated forms of the ubiquitin-conjugating enzyme Ubc6e
… effect of autophagic-related proteins, p62 and ULK1 on Ubc6e. From our research, we saw that Ubc6e levels are reduced when co-expressed with proteins that promote autophagy. Specifically for the autophagy inducer ULK1, we saw differential regulation between the phosphorylated and …
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Mitophagy-Mediated Regulation of ROS Homeostasis During HSC Activation Contributes to Cell Fate
… that HSCs lacking the mammalian Atg1 homologues, ULK1 and ULK2, have a defect in mitophagy but no significant impairment in basal flux through the autophagy pathways to explore the role of mitophagy in HSCs. Despite the comparable increase in mitochondrial content in HSCs lacking Ulk1/2 or Atg7 …
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Identifying Novel Functions of the WNK Pathway
… WNK1 inhibited the unc-51-like kinase 1 (ULK1) complex that acts upstream of PI3KC3. WNK1 also inhibited AMP-activated protein kinase (AMPK), the upstream activator of ULK1. The actions of WNK1 on the AMPK-ULK1 axis only partially mediated its effects on autophagy. WNK1 directly bound UV …
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Estrogen signaling interacts with Sirt1 in adipocyte autophagy
… this difference. Mechanistically, E2-ER- mTOR-ULK1-autophagy signaling contributed to the gender difference in visceral fat distribution. Secondly, in vitro and in vivo studies demonstrated that Sirt1 suppressed autophagy and reduced adipogenesis and adiposity via inducing mTOR-ULK1 signaling. …
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Identification and Targeting of Downstream Ar-Camkk2-Mediated Mechanisms For The Treatment of Advanced Prostate Cancer
… Unc-51 like autophagy activating kinase 1 (ULK1), an important autophagic initiator, as one of downstream effectors regulated by AR-CAMKK2-5’-AMP-activated protein kinase (AMPK) signaling. CAMKK2-induced protective autophagy is partially dependent on the phosphorylation of ULK1 at serine …
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Autophagy and Lipid Homeostasis in C. elegans
… discovered that autophagy gene activity (unc-51/ULK1/2, bec-1/BECN1, vps-34/VPS34, and lgg-1/LC3I) is required for neutral lipid accumulation during development in C. elegans. Moreover, long-lived, daf-2/InR and glp-1/Notch loss of function mutants, characterized by increased lipid stores, also …
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Regulation and roles of nutrient-dependent mitochondrial fusion
… This project studied the roles of the Ulk1, AMPK and PKA pathways in amino acid starvation-dependent mitochondrial fusion. Using a metabolomics approach, this project also studied changes in cellular metabolism during amino acid starvation-dependent mitochondrial fusion and how …
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Targeting autophagy for improving stem cell function in brain repair
… alter autophagy in the cells by over-expressing ULK1 or knocking down Atg7. MHP-36 cells showed some markers of increased autophagy in vitro following ULK1 over-expression, but effects were not robust, as compared to parallel tests with other model cell lines (293A HEK). As such, we relied more …
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AMP Deaminase 3 overexpression regulates cellular energetics and signaling for PGC-1α activation.
… AMPK targets, ACC (Ser79, 4.8-fold) and ULK1 (Ser555, 2-fold) (p<0.001). Aspartic acid levels increased 7.1-fold (p<0.001), suggesting decreased activity of the purine nucleotide cycle (IMP + aspartic acid [rightwards arrow][rightwards arrow] AMP). As expected, myotubes that were …
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Regulation of mTORC1 by homocysteine and its effects on autophagy in human and mouse neuronal tissues
… cells, mTORC1 mediates phosphorylation of ULK1 which consequently reduces LC3 lipidation. mTORC1 also dampens TFEB-driven transcription of autophagy-related genes resulting in a buildup of abnormal proteins, including [beta]-amyloid and phospho-Tau. Formation of these protein aggregates …
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Regulation of the Lipid Kinase VPS34 by mTOR-Mediated UVRAG Phosphorylation
… autophagy in combination with the protein kinase ULK1. Autophagy acts as a catabolic pathway that is up regulated in response to stress, but is negatively regulated by the master growth protein kinase mTOR. This study sought to identify novel control mechanisms that may mediate the regulation of …
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Investigation of mTOR-independent regulation of macroautophagy
… of the key autophagy regulators ATG13, ULK1, ATG14 and TFEB. Consequently, mTORC1 has become a candidate therapeutic target in neurodegeneration and cancer; however, its essential role in other cellular programs has prompted the investigation of mTORC1-independent regulation of …
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The Role Of ROS-mediated ERK and JNK Activation In The Induction Of Autophagy And Apoptosis In Tumour Cells By A Novel Small Molecule Compound
… against autophagy or cell death, Atg 7 or Ulk1 knock-down significantly abrogated C1-induced autophagy. In the current study, the induction of autophagy and apoptosis was found to be mutually exclusive. Despite this fact, early H2O2 production was critical in controlling the induction of …
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Understanding The Role of Sumoylation In Regulating Lkb1 Function
… acid oxidation), mTORC1 (protein synthesis), ULK1 (mitophagy) and GLUT1 (glucose uptake). Therefore, LKB1 is strategically positioned as an essential kinase in maintaining cellular energy balance.</p> <p>A number of studies have described the influence of covalent post-translational …
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TRPML1: Role In Autophagy And Potential Target To Treat Lysosomal Storage Disorders
… involved in autophagy initiation such as ULK1 and PIK3C3 complexes. In parallel studies, we used high content (HC) screening approaches to identify small molecules able to ameliorate the MLIV phenotype. In one of them, we tested whether previously identified drugs (150 FDA compounds) …
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