Article

Autophagy: A Forty-Year Search for a Missing Membrane Source

Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota, USA.
PLoS Biology (Impact Factor: 9.34). 03/2006; 4(2):e36. DOI: 10.1371/journal.pbio.0040036
Source: PubMed

ABSTRACT

Autophagy is central to diverse biological processes in eukaryotes including animal development and cellular survival, and also to neurodegenerative diseases, but the origin of the membranes that make up autophagic vesicles is unknown.

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    • "Inactivation in times of nutrient deprivation or cellular stress triggers the formation of an isolation membrane from cellular apparatus including the endoplasmic reticulum [12] and the sequestration of cytoplasmic material to be degraded into a double membraned autophagosome [9]. Subsequent fusion of the autophagosome with a lysosome then results in the formation of an autolysosome where cytosolic components are broken-down to free building blocks that are later recycled to sustain cellular homeostasis [9]. "
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    ABSTRACT: Half a million new head and neck cancers are diagnosed each year worldwide. Although traditionally thought to be triggered by alcohol and smoking abuse, there is a growing subset of oropharyngeal cancers driven by the oncogenic human papilloma virus (HPV). Despite advances in both surgical and non-surgical treatment strategies, survival rates have remained relatively static emphasising the need for novel therapeutic approaches. Autophagy, the principal catabolic process for the lysosomal – mediated breakdown of cellular products is a hot topic in cancer medicine. Increasing evidence points towards the prognostic significance of autophagy biomarkers in solid tumours as well as strategies through which to harness autophagy modulation to promote tumour cell death. However, the role of autophagy in head and neck cancers is less well defined. In the present review, we summarise the current understanding of autophagy in head and neck cancers, revealing key areas for future translational research.
    Full-text · Article · Jan 2016
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    • "During the induction of autophagy, the isolation membrane (phagophore) elongates and seals itself to produce an autophagosome3,12,46. The autophagosome fuses with endocytic cargos to generate a mature autophagosome. "
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    ABSTRACT: WASH (Wiskott-Aldrich syndrome protein (WASP) and SCAR homolog) was identified to function in endosomal sorting via Arp2/3 activation. We previously demonstrated that WASH is a new interactor of BECN1 and present in the BECN1-PIK3C3 complex with AMBRA1. The AMBRA1-DDB1-CUL4A complex is an E3 ligase for K63-linked ubiquitination of BECN1, which is required for starvation-induced autophagy. WASH suppresses autophagy by inhibition of BECN1 ubiquitination. However, how AMBRA1 is regulated during autophagy remains elusive. Here, we found that RNF2 associates with AMBRA1 to act as an E3 ligase to ubiquitinate AMBRA1 via K48 linkage. RNF2 mediates ubiquitination of AMBRA1 at lysine 45. Notably, RNF2 deficiency enhances autophagy induction. Upon autophagy induction, RNF2 potentiates AMBRA1 degradation with the help of WASH. WASH deficiency impairs the association of RNF2 with AMBRA1 to impede AMBRA1 degradation. Our findings reveal another novel layer of regulation of autophagy through WASH recruitment of RNF2 for AMBRA1 degradation leading to downregulation of autophagy.Cell Research advance online publication 1 July 2014; doi:10.1038/cr.2014.85.
    Full-text · Article · Jul 2014 · Cell Research
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    • "During the main pathway of autophagy, initially appearing membrane cisterns called phagophores capture portions of the cytoplasm in double-membrane autophagosomes. These vesicles then deliver cargo for lysosomal degradation [16,17]. Beclin 1, LC3II and p62 are considered to be the most important molecules during this process, and they are known as autophagy marker genes. "
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    ABSTRACT: Background Recent findings indicated that Derlin-1 has an important function in tumour progression. In this study, we aimed to determine whether Derlin-1 has an oncogene function as a cross-talk molecule with autophagy. Methods Cancer cells were treated with tunicamycin (TM) for 8 and 24 h. The expression of Derlin-1 and autophagy-related genes was determined by western blot. Autophagy was analysed by fluorescence microscopy after staining the cancer cells with monodansylcadaverine. The interaction between Derlin-1 and other proteins was identified using co-immunoprecipitation assay. Results Our study demonstrated high Derlin-1 expression levels in most non-small lung cancer cell lines. Derlin-1 expression was enhanced under endoplasmic reticulum (ER) stress. Previous studies revealed that TM triggers the initiation of autophagy by activating Beclin 1, converting LC3I to LC3II and degrading p62. Knockdown of Derlin-1 did not affect Beclin 1 and LC3II expression but disrupted the degradation of p62 under ER stress, which resulted in the blockage of autophagy flux. Furthermore, Derlin-1 and p62 were observed to interact under ER stress. Conclusion This study is the first report about the interaction between Derlin-1 and p62. Derlin-1 may function in tumour progression partially by interacting with p62.
    Full-text · Article · Jun 2014 · Cancer Cell International
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