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Selective autophagy

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https://www.readbyqxmd.com/read/28544335/p62-sequestosome-1-in-human-colorectal-carcinoma-as-a-potent-prognostic-predictor-associated-with-cell-proliferation
#1
Shun Nakayama, Hideaki Karasawa, Takashi Suzuki, Shinichi Yabuuchi, Kiyoshi Takagi, Takashi Aizawa, Yoshiaki Onodera, Yasuhiro Nakamura, Mika Watanabe, Fumiyoshi Fujishima, Hiroshi Yoshida, Takanori Morikawa, Tomohiko Sase, Takeshi Naitoh, Michiaki Unno, Hironobu Sasano
p62/sequestosome 1 (p62) is a multi-domain protein that functions as a receptor for ubiquitinated targets in the selective autophagy and serves as a scaffold in various signaling cascades. p62 have been reported to be up-regulated in several human malignancies, but the biological roles and significance of p62 are still poorly understood in colorectal carcinoma. We immunohistochemically evaluated p62 in 118 colorectal adenocarcinoma and 28 colorectal adenoma cases. We used four colon carcinoma cells (HCT8, HT29, COLO320, and SW480) in the in vitro studies...
May 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28542236/sphingolipids-as-a-new-factor-in-the-pathomechanism-of-preeclampsia-mass-spectrometry-analysis
#2
Karol Charkiewicz, Joanna Goscik, Agnieszka Blachnio-Zabielska, Grzegorz Raba, Agata Sakowicz, Jaroslaw Kalinka, Adrian Chabowski, Piotr Laudanski
OBJECTIVE(S) AND DESIGN: The aim of the study was to analyse a panel of 11 sphingolipids in plasma and three blood fractions (platelet-poor plasma, platelets and red blood cells) of women with mild preeclampsia. MATERIALS AND METHODS: We recruited 21 women between 25-40 weeks gestation with diagnosed mild preeclampsia to the study group and 36 healthy women with uncomplicated pregnancies, who corresponded with the study group according to gestational age, to the control group...
2017: PloS One
https://www.readbyqxmd.com/read/28533411/bidirectional-regulation-of-a%C3%AE-levels-by-presenilin-1
#3
Victor Bustos, Maria V Pulina, Yildiz Kelahmetoglu, Subhash C Sinha, Fred S Gorelick, Marc Flajolet, Paul Greengard
Alzheimer's disease (AD) is characterized by accumulation of the β-amyloid peptide (Aβ), which is generated through sequential proteolysis of the amyloid precursor protein (APP), first by the action of β-secretase, generating the β-C-terminal fragment (βCTF), and then by the Presenilin 1 (PS1) enzyme in the γ-secretase complex, generating Aβ. γ-Secretase is an intramembranous protein complex composed of Aph1, Pen2, Nicastrin, and Presenilin 1. Although it has a central role in the pathogenesis of AD, knowledge of the mechanisms that regulate PS1 function is limited...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533369/phosphorylated-presenilin-1-decreases-%C3%AE-amyloid-by-facilitating-autophagosome-lysosome-fusion
#4
Victor Bustos, Maria V Pulina, Ashley Bispo, Alison Lam, Marc Flajolet, Fred S Gorelick, Paul Greengard
Presenilin 1 (PS1), the catalytic subunit of the γ-secretase complex, cleaves βCTF to produce Aβ. We have shown that PS1 regulates Aβ levels by a unique bifunctional mechanism. In addition to its known role as the catalytic subunit of the γ-secretase complex, selective phosphorylation of PS1 on Ser367 decreases Aβ levels by increasing βCTF degradation through autophagy. Here, we report the molecular mechanism by which PS1 modulates βCTF degradation. We show that PS1 phosphorylated at Ser367, but not nonphosphorylated PS1, interacts with Annexin A2, which, in turn, interacts with the lysosomal N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) Vamp8...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28531150/distinct-contributions-of-autophagy-receptors-in-measles-virus-replication
#5
Denitsa S Petkova, Pauline Verlhac, Aurore Rozières, Joël Baguet, Mathieu Claviere, Carole Kretz-Remy, Renaud Mahieux, Christophe Viret, Mathias Faure
Autophagy is a potent cell autonomous defense mechanism that engages the lysosomal pathway to fight intracellular pathogens. Several autophagy receptors can recognize invading pathogens in order to target them towards autophagy for their degradation after the fusion of pathogen-containing autophagosomes with lysosomes. However, numerous intracellular pathogens can avoid or exploit autophagy, among which is measles virus (MeV). This virus induces a complete autophagy flux, which is required to improve viral replication...
May 22, 2017: Viruses
https://www.readbyqxmd.com/read/28531143/a-4-phenoxyphenol-derivative-exerts-inhibitory-effects-on-human-hepatocellular-carcinoma-cells-through-regulating-autophagy-and-apoptosis-accompanied-by-downregulating-%C3%AE-tubulin-expression
#6
Wen-Tsan Chang, Wangta Liu, Yi-Han Chiu, Bing-Hung Chen, Shih-Chang Chuang, Yen-Chun Chen, Yun-Tzh Hsu, Mei-Jei Lu, Shean-Jaw Chiou, Chon-Kit Chou, Chien-Chih Chiu
Hepatocellular carcinoma (HCC) is a leading cancer worldwide. Advanced HCCs are usually resistant to anticancer drugs, causing unsatisfactory chemotherapy outcomes. In this study, we showed that a 4-phenoxyphenol derivative, 4-[4-(4-hydroxyphenoxy)phenoxy]phenol (4-HPPP), exerts an inhibitory activity against two HCC cell lines, Huh7 and Ha22T. We further investigated the anti-HCC activities of 4-HPPP, including anti-proliferation and induction of apoptosis. Our results showed that higher dosage of 4-HPPP downregulates the expression of α-tubulin and causes nuclear enlargement in both the Huh-7 and Ha22T cell lines...
May 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28530014/microrna-30a-5p-promotes-replication-of-porcine-circovirus-type-2-through-enhancing-autophagy-by-targeting-14-3-3
#7
Xiaomin Wang, Xianglan Xu, Wei Wang, Zhengyu Yu, Libin Wen, Kongwang He, Hongjie Fan
Accumulating evidence demonstrates that autophagy and microRNAs (miRNAs) play key roles in regulating virus-host interactions and can restrict or facilitate viral replication. In the present study we examined whether a functional relationship exists between autophagy, miRNA and porcine circovirus type 2 (PCV2) infection, using several approaches. We demonstrated that there was a positive correlation between PCV2 infection and autophagy in 3D4/21 cells and autophagy induced by PCV2 infection triggered PCV2 replication...
May 22, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28529589/tetrandrine-triggers-an-alternative-autophagy-in-du145-cells
#8
Wei Qiu, Ai-Li Zhang, Ye Tian
Tetrandrine (Tet), a potent lysosomal inhibitor, blocks autophagic flux and induces cancer cell death. Previously, the present authors identified the prostate cancer cell line DU145 to exhibit high sensitivity towards Tet in 11 cancer cell lines. In the present study, autophagy in Tet-treated DU145 cells was investigated. Similar to other cell lines, such as PC-3 and 786-O cells, Tet neutralized the acidity of lysosome and blocked autophagy in DU145 cells. However, Tet failed to induce microtubule-associated protein 1 light chain 3 (LC3) conversion in DU145 cells...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28528975/autophagy-related-gene-microarray-and-bioinformatics-analysis-for-ischemic-stroke-detection
#9
Yinsheng Guo, Yue Ma, Yanwei Zhang, Li Zhou, Suli Huang, Ying Wen, Fei Zou, Jinquan Cheng
Ischemic stroke (IS) is characterized by high morbidity and poor prognosis. However, the mechanisms of IS induced injury are still poorly understood. The main aim of this study is to explore the role of autophagy in IS. Ten pairs of whole blood samples of IS patients and matched controls were included to select differential expressed genes (DE genes) by autophagy-related functional gene microarray analysis. And then, one hundred and fifty pairs of whole blood samples of IS patients and matched controls were included to validate the DE genes...
May 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28528166/regulation-of-nutrient-recycling-via-autophagy
#10
REVIEW
Céline Masclaux-Daubresse, Qinwu Chen, Marien Havé
Autophagy is a universal mechanism in eukaryotes that promotes cell longevity and nutrient recycling through the degradation of unwanted organelles, proteins and damaged cytoplasmic compounds. Autophagy is important in plant resistance to stresses and starvations and in remobilization. Autophagy facilitates bulk and selective degradations, through the delivery of cell material to the vacuole where hydrolases and proteases reside. Large metabolite modifications are observed in autophagy mutants showing the important role of autophagy in cell homeostasis...
May 18, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28526861/shedding-of-host-autophagic-proteins-from-the-parasitophorous-vacuolar-membrane-of-plasmodium-berghei
#11
Carolina Agop-Nersesian, Mariana De Niz, Livia Niklaus, Monica Prado, Nina Eickel, Volker T Heussler
The hepatic stage of the malaria parasite Plasmodium is accompanied by an autophagy-mediated host response directly targeting the parasitophorous vacuolar membrane (PVM) harbouring the parasite. Removal of the PVM-associated autophagic proteins such as ubiquitin, p62, and LC3 correlates with parasite survival. Yet, it is unclear how Plasmodium avoids the deleterious effects of selective autophagy. Here we show that parasites trap host autophagic factors in the tubovesicular network (TVN), an expansion of the PVM into the host cytoplasm...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526691/zinc-deficiency-an-unexpected-trigger-for-autophagy
#12
Binbin Ding, Qing Zhong
Cells respond to deprivation of certain nutrients such as glucose or nitrogen by inducing autophagy, reclaiming pieces of proteins for use in critical functions. A recent study shows that, in yeast, zinc depletion acts in a similar fashion. Depletion of this essential nutrient induces non-selective autophagy by inhibiting TORC1, leading to release and recycling of zinc from degraded proteins.
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28525743/bromodomain-protein-brd4-is-a-transcriptional-repressor-of-autophagy-and-lysosomal-function
#13
Jun-Ichi Sakamaki, Simon Wilkinson, Marcel Hahn, Nilgun Tasdemir, Jim O'Prey, William Clark, Ann Hedley, Colin Nixon, Jaclyn S Long, Maria New, Tim Van Acker, Sharon A Tooze, Scott W Lowe, Ivan Dikic, Kevin M Ryan
Autophagy is a membrane-trafficking process that directs degradation of cytoplasmic material in lysosomes. The process promotes cellular fidelity, and while the core machinery of autophagy is known, the mechanisms that promote and sustain autophagy are less well defined. Here we report that the epigenetic reader BRD4 and the methyltransferase G9a repress a TFEB/TFE3/MITF-independent transcriptional program that promotes autophagy and lysosome biogenesis. We show that BRD4 knockdown induces autophagy in vitro and in vivo in response to some, but not all, situations...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28522553/glioblastoma-derived-cells-in-vitro-unveil-the-spectrum-of-drug-resistance-capabilty-comparative-study-of-tumour-chemosensitivity-in-different-culture-systems
#14
Monika Witusik-Perkowska, Magdalena Zakrzewska, Beata Sikorska, Wielislaw Papierz, Dariusz J Jaskolski, Janusz Szemraj, Pawel P Liberski
Resistance to cancer drugs is a complex phenomenon which could be influenced by in vitro conditions. However, tumour-derived cell cultures are routinely used for studies related to mechanisms of drug responsiveness or the search for new therapeutic approaches. The purpose of our work was to identify the potential differences in drug resistance and response to treatment of glioblastoma with the use of three in vitro models: traditional adherent culture, serum-free spheroid culture and novel adherent serum-free culture...
May 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28521612/the-peroxisomal-aaa-atpase-complex-prevents-pexophagy-and-development-of-peroxisome-biogenesis-disorders
#15
Kelsey B Law, Dana Bronte-Tinkew, Erminia Di Pietro, Ann Snowden, Richard O Jones, Ann Moser, John H Brumell, Nancy Braverman, Peter K Kim
Peroxisome biogenesis disorders (PBDs) are metabolic disorders caused by the loss of peroxisomes. The majority of PBDs result from mutation in one of 3 genes that encode for the peroxisomal AAA ATPase complex (AAA-complex) required for cycling PEX5 for peroxisomal matrix protein import. Mutations in these genes are thought to result in a defect in peroxisome assembly by preventing the import of matrix proteins. However, we show here that loss of the AAA-complex does not prevent matrix protein import, but instead causes an upregulation of peroxisome degradation by macroautophagy, or pexophagy...
May 4, 2017: Autophagy
https://www.readbyqxmd.com/read/28521459/cisplatin-regulates-cell-autophagy-in-endometrial-cancer-cells-via-the-pi3k-akt-mtor-signalling-pathway
#16
Qiongyan Lin, Yifeng Wang, Dunjin Chen, Xiujie Sheng, Juan Liu, Hanzhen Xiong
Endometrial cancer is the most common gynaecological malignancy encountered in developed countries and the second most common in the developing world. The five-year survival rate of patients with endometrial cancer diagnosed at a late stage is <30%. Therefore, it is critical to develop a suitable chemotherapeutic regimen for late-stage endometrial cancer. Cisplatin (CDDP) is a first-line chemotherapeutic drug for endometrial cancer chemotherapy. The present study investigated the molecular mechanism underlying the effect of CDDP on endometrial cancer from the perspective of cell autophagy...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28518135/rack1-depletion-in-the-ribosome-induces-selective-translation-for-non-canonical-autophagy
#17
Hag Dong Kim, EunBin Kong, YongJoong Kim, Jin-Soo Chang, Joon Kim
RACK1, which was first demonstrated as a substrate of PKCβ II, functions as a scaffold protein and associates with the 40S small ribosomal subunit. According to previous reports, ribosomal RACK1 was also suggested to control translation depending on the status in translating ribosome. We here show that RACK1 knockdown induces autophagy independent of upstream canonical factors such as Beclin1, Atg7 and Atg5/12 conjugates. We further report that RACK1 knockdown induces the association of mRNAs of LC3 and Bcl-xL with polysomes, indicating increased translation of these proteins...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28513333/atg9a-deficiency-causes-axon-specific-lesions-including-neuronal-circuit-dysgenesis
#18
Junji Yamaguchi, Chigure Suzuki, Tomohisa Nanao, Soichirou Kakuta, Kentarou Ozawa, Isei Tanida, Tatsuya Saitoh, Takehiko Sunabori, Masaaki Komatsu, Keiji Tanaka, Shigeki Aoki, Kenji Sakimura, Yasuo Uchiyama
Conditional knockout mice for Atg9a, specifically in brain tissue, were generated to understand the roles of ATG9A in the neural tissue cells. The mice were born normally, but half of them died within one week, and none lived beyond 4 weeks of age. SQSTM1/p62 and NBR1, receptor proteins for selective autophagy, together with ubiquitin, accumulated in Atg9a-deficient neurosoma at postnatal day 15 (P15), indicating an inhibition of autophagy, whereas these proteins were significantly decreased at P28, as evidenced by immunohistochemistry, electron microscopy and western blot...
May 17, 2017: Autophagy
https://www.readbyqxmd.com/read/28504722/thyroid-hormone-protects-hepatocytes-from-hbx-induced-carcinogenesis-by-enhancing-mitochondrial-turnover
#19
H-C Chi, S-L Chen, S-L Lin, C-Y Tsai, W-Y Chuang, Y-H Lin, Y-H Huang, M-M Tsai, C-T Yeh, K-H Lin
Infection by hepatitis B virus (HBV) accounts for 50-80% of hepatocellular carcinoma (HCC) development worldwide, in which the HBV-encoded X protein (HBx) has critical role in the induction of carcinogenesis. Several studies have shown that thyroid hormone (TH) suppresses HCC development and protects hepatocytes from HBx-induced damage, thus it is of interest to examine whether TH can protect hepatocytes from HBx-induced carcinogenesis. By treating HBx- transgenic mice with or without TH, we confirmed the protective effects of TH on HBx-induced hepatocarcinogenesis, which was achieved via reduction of reactive oxygen species (ROS) inflicted DNA damage...
May 15, 2017: Oncogene
https://www.readbyqxmd.com/read/28504708/receptor-oligomerization-guides-pathway-choice-between-proteasomal-and-autophagic-degradation
#20
Kefeng Lu, Fabian den Brave, Stefan Jentsch
Abnormal or aggregated proteins have a strong cytotoxic potential and are causative for human disorders such as Alzheimer's, Parkinson's, Huntington's disease and amyotrophic lateral sclerosis. If not restored by molecular chaperones, abnormal proteins are typically degraded by proteasomes or eliminated by selective autophagy. The discovery that both pathways are initiated by substrate ubiquitylation but utilize different ubiquitin receptors incited a debate over how pathway choice is achieved. Here, we demonstrate in yeast that pathway choice is made after substrate ubiquitylation by competing ubiquitin receptors harbouring either proteasome- or autophagy-related protein 8 (Atg8/LC3)-binding modules...
May 15, 2017: Nature Cell Biology
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