A ubiquitin-like system mediates protein lipidation

Ichimura, Yoshinobu; Kirisako, Takayoshi; Takao, Toshifumi; Satomi, Yoshinori; Shimonishi, Yasutsugu; Ishihara, Naotada; Mizushima, Noboru; Tanida, Isei; Kominami, Eiki; Ohsumi, Mariko; Noda, Tetsuji; Ohsumi, Yoshinori

doi:10.1038/35044114

Cited by 1,803 publications

(1,574 citation statements)

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“…Both Beclin-1 and ATG7 are genes essential for the induction of autophagy (Ichimura et al, 2000;Tassa et al, 2003). Reduction of Beclin-1 protein levels was confirmed by western blot analysis and reduction of ATG7 mRNA levels was confirmed by reverse transcription (RT)-PCR (Figures 5b and c).…”

Section: Six Transmembrane Domains Of Lmp1 Induce Autophagy Dy Lee Anmentioning

confidence: 70%

The latent membrane protein 1 oncogene modifies B-cell physiology by regulating autophagy

2007

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Epstein-Barr virus (EBV) is a herpes virus that is associated with several human cancers. Infection of B cells by EBV leads to their induction and maintenance of proliferation and requires the oncogene, latent membrane protein 1 (LMP1). LMP1 signals in a ligand-independent manner and is expressed at widely different levels in cells of a single clone. It is this unusual distribution that allows LMP1 to stimulate multiple, distinct pathways. Average levels of LMP1 induce proliferation while high levels induce cytostasis and inhibition of protein synthesis. These inhibitory pathways are induced by the six transmembrane domains of LMP1. We uncovered a novel function encoded by transmembrane domains 3-6 of LMP1; they induce autophagy in a dose-dependent manner and thus, modify the physiology of their host. Cells that express low levels of LMP1 display early stages of autophagy, autophagosomes; those that express high levels of this oncogene display late stages of autophagy, autolysosomes. Inhibition of autophagy in EBV-positive cells leads to an accumulation of LMP1 and a decreased ability to form colonies. These results indicate that LMP1's induction of autophagy contributes to its own regulation and that of its host cell.

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Section: Six Transmembrane Domains Of Lmp1 Induce Autophagy Dy Lee Anmentioning

confidence: 70%

The latent membrane protein 1 oncogene modifies B-cell physiology by regulating autophagy

2007

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“…Cleavage of LC3 at the carboxy terminus immediately following synthesis yields the cytosolic LC3‐I form. During autophagy, LC3‐I is converted to LC3‐II through lipidation (the covalent binding of a lipid group to a peptide chain) by an ubiquitin‐like system involving Atg7 and Atg3 that allows LC3 to become associated with autophagic vesicles 12. The ratio of LC3‐II/LC3‐I has been used as an indicator of autophagy 13.…”

Section: Methodsmentioning

confidence: 99%

Role of Autophagy and Apoptosis in Wound Tissue of Deep Second‐degree Burn in Rats

Xiao

et al. 2014

Acad Emerg Med

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ObjectivesThe pathogenesis of burn wound progression is poorly understood. Contributing factors include continuous loss of blood perfusion, excessive inflammation, and elevated apoptosis levels in wound tissue. Macroautophagy (here referred to simply as “autophagy”) is associated with many chronic diseases. The authors hypothesized that autophagy is involved in burn wound progression in a rat model of deep second‐degree burn.MethodsDeep second‐degree burns were modeled using a brass rod heated to 100°C applied for 6 seconds to the back skin of Wistar rats. Full‐thickness biopsies were obtained from burned and nonburned controls at several times postburn. Western blotting and immunohistochemical (IHC) staining determined expression of the autophagy markers Light Chain 3 (LC3) and beclin‐1. Apoptosis was determined by terminal‐deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay and laser Doppler flowmetry (LDF)‐measured tissue perfusion. Myeloperoxidase (MPO) activity assay measured inflammation. Hematoxylin and eosin (H&E) and Masson's trichrome staining–determined pathology and wound depth.ResultsThe LC3 and beclin‐1 protein level in burn wounds decreased to one‐fourth of normal levels (p < 0.01) over 24 hours and then began to increase but still did not reach their normal level. TUNEL‐positive cells in burn wounds were 3.7‐fold (p < 0.01) elevated over 48 hours and then decreased slightly, yet still remained higher than in normal skin. The burn wound progressed in depth over 72 hours. In addition, significant decrease in LDF values and upregulation of MPO activity were observed. Enhanced LC3‐positive cells were observed in the deep dermal layer of burn wounds as shown by IHC staining.ConclusionsA reduction in autophagy and blood flow and an increase in apoptosis and inflammation were observed in burn wounds early during the course of burn injury progression. This suggests that autophagy, complemented by apoptosis, play important roles in burn progression. Enhanced autophagy in the deep dermis may be a prosurvival mechanism against ischemia and inflammation after burn injury.

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“…Atg8 and Atg12 are both activated for conjugation by Atg7, an E1-like enzyme of the ubiquitin system. 18,19 Atg9 is the only currently characterized transmembrane protein involved in the formation of double-membrane vesicles, and is thought to mark membranes to be donated to the PAS. 20 Atg1 regulates the shuttling of Atg9 between the PAS and a peripheral pool and in this way is thought to control retrieval of Atg9 and the associated membrane 20 (Figure 2).…”

Section: Macroautophagy In Yeast Is a Multistep Process That Is Regulmentioning

confidence: 99%

Macroautophagy versus mitochondrial autophagy: a question of fate?

Kundu

Thompson²

2005

Cell Death Differ

106

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Autophagy is a catabolic process that allows recycling of cytoplasmic components (including organelles) into basic components, offering a bioenergetically efficient alternative to de novo synthesis. In yeast, autophagy functions primarily as an adaptive mechanism allowing survival in the response to changes in the availability of nutrients in the environment. Over the past decade, genetic screens performed in yeast have elucidated many of the molecular components involved in this adaptive response. [1][2][3] More recently, the roles of homologous genes are being explored in multicellular organisms and in cells derived from these organisms. 4 These studies have demonstrated that while autophagy is often induced as part of an adaptive response, induction of autophagy may also lead to cell death. During Drosophila larval development, for example, starvation-induced autophagy occurs in the larval fat body and is required for maintaining circulating nutrient levels and survival of the larvae under unfavorable nutritional conditions; 5 by contrast, programmed autophagy results in cell death and is the primary means of removing certain larval organs during metamorphosis. 6 On a cellular level, autophagy is observed prior to apoptosis in growth factor-deprived neuronal cultures. 7,8 In cells lacking critical proapoptotic proteins, the adaptive process of autophagy aimed at maintaining bioenergetic homeostasis can be unmasked in response to growthfactor withdrawal. 9 In contrast, cell death in response to a variety of chemicals has been suggested to result from autophagic destruction of the cell and to be suppressed by inhibition of autophagy. 10 The factors that determine whether induction of autophagy contributes to cell survival or cell death are not well-elucidated; however, two key issues may be the rate of autophagic degradation and the specificity of the engulfed components. Although autophagy is generally considered a nonspecific process, there are instances where the mitochondria (and other organelles) appear to be specifically targeted. Here, we focus on the signals and pathways involved in regulating the induction of autophagy and mitochondrial autophagy in yeast and how these processes are relevant to survival and death of mammalian cells.In general terms, 'autophagy' refers to any intracellular process that involves the degradation of cytosolic components by the lysosome. There are at least three distinct autophagic pathways: macroautophagy, microautophagy and chaperone-mediated autophagy. Macroautophagy is a multistep process by which portions of cytoplasm and/or organelles are sequestered in a double or multimembrane structure ('autophagosome') and delivered to the lysosome for degradation (Figure 1). Upon fusion of the autophagosome with the lysosome, it becomes an autophagolysosome or autophagic vacuole. Although macroautophagy is generally considered a nonspecific process there are instances in which organelles, such as mitochondria and peroxisomes, appear to be preferentially sequestered. These process...

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A ubiquitin-like system mediates protein lipidation

Cited by 1,803 publications

References 26 publications

The latent membrane protein 1 oncogene modifies B-cell physiology by regulating autophagy

The latent membrane protein 1 oncogene modifies B-cell physiology by regulating autophagy

Role of Autophagy and Apoptosis in Wound Tissue of Deep Second‐degree Burn in Rats

Macroautophagy versus mitochondrial autophagy: a question of fate?

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