Emneord:
Hjernen og nervesystemet,
Kreft,
Cellebiologi,
Membrantransport,
Autofagi,
Nevrodegenerative sykdommer,
Livsvitenskap
Publikasjoner
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Sikkeland, Jørgen; Ng, Matthew; Nenseth, Hatice Zeynep; Ünal, Bilal; Qu, Su & Jin, Yang
[Vis alle 8 forfattere av denne artikkelen]
(2022).
STAMP2 suppresses autophagy in prostate cancer cells by modulating the integrated stress response pathway.
American Journal of Cancer Research.
ISSN 2156-6976.
12(1),
s. 327–336.
Fulltekst i vitenarkiv
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Charsou, Chara; Ng, Matthew & Simonsen, Anne Gjøen
(2022).
Regulation of autophagosome biogenesis and mitochondrial bioenergetics by the cholesterol transport protein GRAMD1C.
Autophagy.
ISSN 1554-8627.
doi:
10.1080/15548627.2022.2155020.
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Cable, Jennifer; Weber-Ban, Eilika; Clausen, Tim; Walters, Kylie J.; Sharon, Michal & Finley, Daniel J.
[Vis alle 32 forfattere av denne artikkelen]
(2022).
Targeted protein degradation: from small molecules to complex organelles—a Keystone Symposia report.
Annals of the New York Academy of Sciences.
ISSN 0077-8923.
1510(1),
s. 79–99.
doi:
10.1111/nyas.14745.
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Terešak, Petra; Da Silva Lapao, Ana Sofia; Subic, Nemanja; Boya, Patricia; Elazar, Zvulun & Simonsen, Anne Gjøen
(2021).
Regulation of PRKN-independent mitophagy.
Autophagy.
ISSN 1554-8627.
18(1),
s. 24–39.
doi:
10.1080/15548627.2021.1888244.
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Corkery, Dale P.; Nadeem, Aftab; Aung, Kyaw Min; Hassan, Ahmed; Liu, Tao & Cervantes-Rivera, Ramón
[Vis alle 14 forfattere av denne artikkelen]
(2021).
Vibrio cholerae cytotoxin MakA induces noncanonical autophagy resulting in the spatial inhibition of canonical autophagy.
Journal of Cell Science.
ISSN 0021-9533.
134(5).
doi:
10.1242/jcs.252015.
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Kumar, Suresh; Javed, Ruheena; Mudd, Michal H.; Pallikkuth, Sandeep; Lidke, Keith A. & Jain, Ashish
[Vis alle 22 forfattere av denne artikkelen]
(2021).
Mammalian hybrid pre-autophagosomal structure HyPAS generates autophagosomes.
Cell.
ISSN 0092-8674.
184(24),
s. 5950–5969.
doi:
10.1016/j.cell.2021.10.017.
Vis sammendrag
The biogenesis of mammalian autophagosomes remains to be fully defined. Here, we used cellular and in vitro membrane fusion analyses to show that autophagosomes are formed from a hitherto unappreciated hybrid membrane compartment. The autophagic precursors emerge through fusion of FIP200 vesicles, derived from the cis-Golgi, with endosomally derived ATG16L1 membranes to generate a hybrid pre-autophagosomal structure, HyPAS. A previously unrecognized apparatus defined here controls HyPAS biogenesis and mammalian autophagosomal precursor membranes. HyPAS can be modulated by pharmacological agents whereas its formation is inhibited upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or by expression of SARS-CoV-2 nsp6. These findings reveal the origin of mammalian autophagosomal membranes, which emerge via convergence of secretory and endosomal pathways, and show that this process is targeted by microbial factors such as coronaviral membrane-modulating proteins
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Ng, Matthew; Wai, Timothy & Simonsen, Anne Gjøen
(2021).
Quality control of the mitochondrion.
Developmental Cell.
ISSN 1534-5807.
56(7),
s. 881–905.
doi:
10.1016/j.devcel.2021.02.009.
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Munson, Michael Joseph; Mathai, Benan J.; Ng, Matthew; Trachsel Moncho, Laura Cristina; de la Ballina, Laura R & Schultz, Sebastian W.
[Vis alle 13 forfattere av denne artikkelen]
(2021).
GAK and PRKCD are positive regulators of PRKN-independent mitophagy.
Nature Communications.
ISSN 2041-1723.
12(1).
doi:
10.1038/s41467-021-26331-7.
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The mechanisms involved in programmed or damage-induced removal of mitochondria by mitophagy remains elusive. Here, we have screened for regulators of PRKN-independent mitophagy using an siRNA library targeting 197 proteins containing lipid interacting domains. We identify Cyclin G-associated kinase (GAK) and Protein Kinase C Delta (PRKCD) as regulators of PRKN-independent mitophagy, with both being dispensable for PRKN- dependent mitophagy and starvation-induced autophagy. We demonstrate that the kinase activity of both GAK and PRKCD are required for efficient mitophagy in vitro, that PRKCD is present on mitochondria, and that PRKCD facilitates recruitment of ULK1/ATG13 to early autophagic structures. Importantly, we demonstrate in vivo relevance for both kinases in the regulation of basal mitophagy. Knockdown of GAK homologue (gakh-1) in C. elegans or knockout of PRKCD homologues in zebrafish led to significant inhibition of basal mitophagy, highlighting the evolutionary relevance of these kinases in mitophagy regulation.
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Gawel, Kinga Aurelia; Turski, Waldemar A.; van der Ent, Wietske; Mathai, Benan John; Kirstein-Smardzewska, Karolina Joanna & Simonsen, Anne
[Vis alle 7 forfattere av denne artikkelen]
(2020).
Phenotypic Characterization of Larval Zebrafish (Danio rerio) with Partial Knockdown of the cacna1a Gene.
Molecular Neurobiology.
ISSN 0893-7648.
57(4).
doi:
10.1007/s12035-019-01860-x.
Vis sammendrag
The CACNA1A gene encodes the pore-forming α1 subunit of voltage-gated P/Q type Ca2+ channels (Cav2.1). Mutations in this gene, among others, have been described in patients and rodents suffering from absence seizures and episodic ataxia type 2 with/without concomitant seizures. In this study, we aimed for the first time to assess phenotypic and behavioral alterations in larval zebrafish with partial cacna1aa knockdown, placing special emphasis on changes in epileptiform-like electrographic discharges in larval brains. Whole-mount in situ hybridization analysis revealed expression of cacna1aa in the optic tectum and medulla oblongata of larval zebrafish at 4 and 5 days post-fertilization. Next, microinjection of two antisense morpholino oligomers (individually or in combination) targeting all splice variants of cacna1aa into fertilized zebrafish eggs resulted in dose-dependent mortality and decreased or absent touch response. Over 90% knockdown of cacna1aa on protein level induced epileptiform-like discharges in the optic tectum of larval zebrafish brains. Incubation of morphants with antiseizure drugs (sodium valproate, ethosuximide, lamotrigine, topiramate) significantly decreased the number and, in some cases, cumulative duration of epileptiform-like discharges. In this context, sodium valproate seemed to be the least effective. Carbamazepine did not affect the number and duration of epileptiform-like discharges. Altogether, our data indicate that cacna1aa loss-of-function zebrafish may be considered a new model of absence epilepsy and may prove useful both for the investigation of Cacna1a-mediated epileptogenesis and for in vivo drug screening.
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Melia, Thomas; Lystad, Alf Håkon & Simonsen, Anne
(2020).
Autophagosome biogenesis: From membrane growth to closure.
Journal of Cell Biology.
ISSN 0021-9525.
219(6).
doi:
10.1083/jcb.202002085.
Fulltekst i vitenarkiv
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Moller, Katrin; Sigurbjornsdottir, Sara; Arnthorsson, Asgeir; Podenberg, Vivian; Dilshat, Ramile & Fock, Valerie
[Vis alle 16 forfattere av denne artikkelen]
(2019).
MITF has a central role in regulating starvation-induced autophagy in melanoma.
Scientific Reports.
ISSN 2045-2322.
9.
doi:
10.1038/s41598-018-37522-6.
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The MITF transcription factor is a master regulator of melanocyte development and a critical factor in melanomagenesis. The related transcription factors TFEB and TFE3 regulate lysosomal activity and autophagy processes known to be important in melanoma. Here we show that MITF binds the CLEAR-box element in the promoters of lysosomal and autophagosomal genes in melanocytes and melanoma cells. The crystal structure of MITF bound to the CLEAR-box reveals how the palindromic nature of this motif induces symmetric MITF homodimer binding. In metastatic melanoma tumors and cell lines, MITF positively correlates with the expression of lysosomal and autophagosomal genes, which, interestingly, are different from the lysosomal and autophagosomal genes correlated with TFEB and TFE3. Depletion of MITF in melanoma cells and melanocytes attenuates the response to starvation-induced autophagy, whereas the overexpression of MITF in melanoma cells increases the number of autophagosomes but is not sufficient to induce autophagic flux. Our results suggest that MITF and the related factors TFEB and TFE3 have separate roles in regulating a starvation-induced autophagy response in melanoma. Understanding the normal and pathophysiological roles of MITF and related transcription factors may provide important clinical insights into melanoma therapy.
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Lystad, Alf Håkon & Simonsen, Anne
(2019).
Mechanisms and Pathophysiological Roles of the ATG8 Conjugation Machinery.
Cells.
ISSN 2073-4409.
8(9).
doi:
10.3390/cells8090973.
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Since their initial discovery around two decades ago, the yeast autophagy-related (Atg)8 protein and its mammalian homologues of the light chain 3 (LC3) and γ-aminobutyric acid receptor associated proteins (GABARAP) families have been key for the tremendous expansion of our knowledge about autophagy, a process in which cytoplasmic material become targeted for lysosomal degradation. These proteins are ubiquitin-like proteins that become directly conjugated to a lipid in the autophagy membrane upon induction of autophagy, thus providing a marker of the pathway, allowing studies of autophagosome biogenesis and maturation. Moreover, the ATG8 proteins function to recruit components of the core autophagy machinery as well as cargo for selective degradation. Importantly, comprehensive structural and biochemical in vitro studies of the machinery required for ATG8 protein lipidation, as well as their genetic manipulation in various model organisms, have provided novel insight into the molecular mechanisms and pathophysiological roles of the mATG8 proteins. Recently, it has become evident that the ATG8 proteins and their conjugation machinery are also involved in intracellular pathways and processes not related to autophagy. This review focuses on the molecular functions of ATG8 proteins and their conjugation machinery in autophagy and other pathways, as well as their links to disease.
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Herzog, Laura K; Kevei, Eva; Marchante, Ricardo; Botther, Claudia; Bindesbøll, Christian & Lystad, Alf Håkon
[Vis alle 12 forfattere av denne artikkelen]
(2019).
The Machado-Joseph disease deubiquitylase ataxin-3 interacts with LC3C/GABARAP and promotes autophagy.
Aging Cell.
ISSN 1474-9718.
doi:
10.1111/acel.13051.
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The pathology of spinocerebellar ataxia type 3, also known as Machado‐Joseph disease, is triggered by aggregation of toxic ataxin‐3 (ATXN3) variants containing expanded polyglutamine repeats. The physiological role of this deubiquitylase, however, remains largely unclear. Our recent work showed that ATX‐3, the nematode orthologue of ATXN3, together with the ubiquitin‐directed segregase CDC‐48, regulates longevity in Caenorhabditis elegans. Here, we demonstrate that the long‐lived cdc‐48.1; atx‐3 double mutant displays reduced viability under prolonged starvation conditions that can be attributed to the loss of catalytically active ATX‐3. Reducing the levels of the autophagy protein BEC‐1 sensitized worms to the effect of ATX‐3 deficiency, suggesting a role of ATX‐3 in autophagy. In support of this conclusion, the depletion of ATXN3 in human cells caused a reduction in autophagosomal degradation of proteins. Surprisingly, reduced degradation in ATXN3‐depleted cells coincided with an increase in the number of autophagosomes while levels of lipidated LC3 remained unaffected. We identified two conserved LIR domains in the catalytic Josephin domain of ATXN3 that directly interacted with the autophagy adaptors LC3C and GABARAP in vitro. While ATXN3 localized to early autophagosomes, it was not subject to lysosomal degradation, suggesting a transient regulatory interaction early in the autophagic pathway. We propose that the deubiquitylase ATX‐3/ATXN3 stimulates autophagic degradation by preventing superfluous initiation of autophagosomes, thereby promoting an efficient autophagic flux important to survive starvation.
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Abudu, Yakubu Princely; Pankiv, Serhiy; Mathai, Benan John; Lamark, Trond; Johansen, Terje & Simonsen, Anne
(2019).
NIPSNAP1 and NIPSNAP2 act as “eat me” signals
to allow sustained recruitment of autophagy
receptors during mitophagy.
Autophagy.
ISSN 1554-8627.
doi:
10.1080/15548627.2019.1637642.
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Johannessen, Tor-Christian Aase; Hasan-Olive, Md Mahdi; Zhu, Huaiyang; Denisova, Oxana V.; Grudic, Amra & Latif, Md Abdul
[Vis alle 20 forfattere av denne artikkelen]
(2018).
Thioridazine inhibits autophagy and sensitizes glioblastoma cells to temozolomide.
International Journal of Cancer.
ISSN 0020-7136.
144(7),
s. 1735–1745.
doi:
10.1002/ijc.31912.
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Aas, Aleksander; Isakson, Pauline; Bindesbøll, Christian; Alemu, Endalkachew Ashenafi; Klungland, Arne & Simonsen, Anne
(2017).
Nucleocytoplasmic shuttling of FTO does not affect starvation-induced autophagy.
PLOS ONE.
ISSN 1932-6203.
12(3).
doi:
10.1371/journal.pone.0168182.
Fulltekst i vitenarkiv
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Dragich, Joanna M; Kuwajima, Takaaki; Hirose-Ikeda, Megumi; Yoon, Michael S; Eenjes, Evelien & Bosco, Joan R
[Vis alle 18 forfattere av denne artikkelen]
(2016).
Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal connectivity in the mammalian brain.
eLIFE.
ISSN 2050-084X.
5(September).
doi:
10.7554/eLife.14810.
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Holland, Petter & Simonsen, Anne
(2015).
Actin shapes the autophagosome.
Nature Cell Biology.
ISSN 1465-7392.
17(9),
s. 1094–1096.
doi:
10.1038/ncb3224.
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Carlsson, Sven R & Simonsen, Anne
(2015).
Membrane dynamics in autophagosome biogenesis.
Journal of Cell Science.
ISSN 0021-9533.
128(2),
s. 193–205.
doi:
10.1242/jcs.141036.
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Lystad, Alf Håkon & Simonsen, Anne
(2015).
Assays to monitor aggrephagy.
Methods.
ISSN 1046-2023.
75,
s. 112–119.
doi:
10.1016/j.ymeth.2014.12.019.
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Holland, Petter; Torgersen, Maria Lyngaas; Sandvig, Kirsten & Simonsen, Anne
(2014).
LYST affects lysosome size and quantity, but not trafficking or degradation through autophagy or endocytosis.
Traffic: The moving front of cell biology.
ISSN 1398-9219.
15(12),
s. 1390–1405.
doi:
10.1111/tra.12227.
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Sengupta, Tanima; Torgersen, Maria Lyngaas; Kassahun, Henok; Vellai, Tibor; Simonsen, Anne & Nilsen, Hilde
(2013).
Base excision repair AP endonucleases and mismatch repair act together to induce checkpoint-mediated autophagy.
Nature Communications.
ISSN 2041-1723.
4.
doi:
10.1038/ncomms3674.
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Isakson, Pauline; Lystad, Alf Håkon; Breen, Kamilla; Koster, Gerbrand; Stenmark, Harald Alfred & Simonsen, Anne
(2013).
TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy.
Autophagy.
ISSN 1554-8627.
9(12),
s. 1955–1964.
doi:
10.4161/auto.26085.
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Knævelsrud, Helene; Carlsson, Sven R & Simonsen, Anne
(2013).
SNX18 tubulates recycling endosomes for autophagosome biogenesis.
Autophagy.
ISSN 1554-8627.
9(10),
s. 1639–1641.
doi:
10.4161/auto.26124.
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Torgersen, Maria Lyngaas & Simonsen, Anne
(2013).
Autophagy: Friend or foe in the treatment of fusion protein-associated leukemias?
Autophagy.
ISSN 1554-8627.
9(12),
s. 2175–2177.
doi:
10.4161/auto.26559.
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Sengupta, Tanima; Torgersen, Maria Lyngaas; Kassahun, Henok; Vellai, Tibor; Simonsen, Anne & Nilsen, Hilde
(2013).
The Base Excision Repair AP-endonucleases functions in the same pathways as Mismatch Repair for Activation of Checkpoint Mediated Autophagy.
Nature Communications.
ISSN 2041-1723.
4.
doi:
10.1038/ncomms3674.
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Knævelsrud, Helene; Søreng, Kristiane; Raiborg, Camilla; Håberg, Karin; Rasmuson, Fredrik & Brech, Andreas
[Vis alle 12 forfattere av denne artikkelen]
(2013).
Membrane remodeling by the PX-BAR protein SNX18 promotes autophagosome formation.
Journal of Cell Biology.
ISSN 0021-9525.
202(2),
s. 331–349.
doi:
10.1083/jcb.201205129.
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Torgersen, Maria Lyngaas; Engedal, Kim Nikolai; Bøe, Stig Ove; Hokland, Peter & Simonsen, Anne
(2013).
Targeting autophagy potentiates the apoptotic effect of histone deacetylase inhibitors in t(8;21) AML cells.
Blood.
ISSN 0006-4971.
122(14),
s. 2467–2476.
doi:
10.1182/blood-2013-05-500629.
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Lång, Emma Helena; Grudic, Amra; Pankiv, Serhiy; Bruserud, Øystein; Simonsen, Anne & Bjerkvig, Rolf
[Vis alle 8 forfattere av denne artikkelen]
(2012).
The arsenic-based cure of acute promyelocytic leukemia promotes cytoplasmic sequestration of PML and PML/RARA through inhibition of PML body recycling.
Blood.
ISSN 0006-4971.
120(4),
s. 847–857.
doi:
10.1182/blood-2011-10-388496.
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Bartlett, Bryan J.; Isakson, Pauline; Lewerenz, Jan; Sanchez, Heriberto; Kotzebue, Roxanne W. & Cumming, Robert C.
[Vis alle 11 forfattere av denne artikkelen]
(2011).
p62, Ref(2)P and ubiquitinated proteins are conserved markers of neuronal aging, aggregate formation and progressive autophagic defects.
Autophagy.
ISSN 1554-8627.
7(6),
s. 572–583.
doi:
10.4161/auto.7.6.14943.
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Yamamoto, Ai & Simonsen, Anne
(2011).
Alfy-dependent elimination of aggregated proteins by macroautophagy Can there be too much of a good thing?
Autophagy.
ISSN 1554-8627.
7(3),
s. 346–350.
doi:
10.4161/auto.7.3.14234.
Se alle arbeider i Cristin
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Bernhoft, Aksel; Brantsæter, Anne Lise; Grøsvik, Bjørn Einar; Harstad, Odd Magne; Holten, Jon Magne & Jenssen, Petter D.
[Vis alle 12 forfattere av denne artikkelen]
(2020).
Hvordan kombinere nok, sunn og trygg mat med bærekraftig produksjon? .
Harvest Magazine.
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Bernhoft, Aksel; Meltzer, Helle Margrete; Holten, Jon Magne; Harstad, Odd Magne; Ytrestøyl, Trine & Mejdell, Cecilie Marie
[Vis alle 12 forfattere av denne artikkelen]
(2020).
Sunn, trygg mat og bærekraftig produksjon – hvilken rolle spiller det hvordan maten blir produsert og hva man spiser for menneskers og jordklodens helse? .
I Havelin, Gro (Red.),
Det norske Videnskaps-akademi Årbok 2019.
Novus Forlag.
ISSN 978-82-7099-925-5.
s. 273–289.
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Lystad, Alf Håkon; Carlsson, Sven R. & Simonsen, Anne
(2019).
Toward the function of mammalian ATG12-ATG5-ATG16L1 complex in autophagy and related processes.
Autophagy.
ISSN 1554-8627.
15(8),
s. 1485–1486.
doi:
10.1080/15548627.2019.1618100.
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The machinery that decorates autophagic membranes with lipid-conjugated LC3/GABARAP is not yet fully understood. We recently reported the purification of the full-length ATG12–ATG5-ATG16L1 complex, and in reconstitution experiments with purified ATG7, ATG3, and LC3/GABARAP in vitro, together with rescue experiments in knockout cells, important aspects of the complete lipidation reaction were revealed. Hitherto unobserved membrane-binding regions in ATG16L1 were found, contributing to properties that explain the crucial role of this protein in membrane targeting and LC3/GABARAP lipidation in macroautophagy/autophagy and other related processes.
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Deretic, Vojo; Prossnitz, Eric; Burge, Mark; Campen, Matthew J.; Cannon, Judy & Liu, Ke Jian
[Vis alle 40 forfattere av denne artikkelen]
(2018).
Autophagy, Inflammation, and Metabolism (AIM) Center of Biomedical Research Excellence: supporting the next generation of autophagy researchers and fostering international collaborations.
Autophagy.
ISSN 1554-8627.
14(6),
s. 925–929.
doi:
10.1080/15548627.2018.1465784.
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Ogmundsdottir, MH; Fock, Valerie; Sooman, L; Pogenberg, Vivian; Dilshat, R & Bindesbøll, Christian
[Vis alle 10 forfattere av denne artikkelen]
(2018).
Erratum to: A short isoform of ATG7 fails to lipidate LC3/GABARAP (Scientific Reports, (2018), 8, 1, (14391), 10.1038/s41598-018-32694-7).
Scientific Reports.
ISSN 2045-2322.
8(1).
doi:
10.1038/s41598-018-35540-y.
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Simonsen, Anne
(2016).
Selvspising forlenger livet.
Tidsskrift for Den norske legeforening.
ISSN 0029-2001.
136(22).
doi:
10.4045/tidsskr.16.0908.
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Klionsky, Daniel J; Abeliovich, Hagai; Agostinis, Patrizia; Agrawal, Devendra K; Aliev, Gjumrakch & Askew, David S
[Vis alle 236 forfattere av denne artikkelen]
(2016).
Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356.
Autophagy.
ISSN 1554-8627.
12(2),
s. 443–443.
doi:
10.1080/15548627.2016.1147886.
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Torgersen, Maria Lyngaas & Simonsen, Anne
(2013).
Friend or foe in the treatment of fusion protein-associated leukemias?
Autophagy.
ISSN 1554-8627.
9(12),
s. 2175–2177.
doi:
10.4161/auto.26559.
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Simonsen, Anne & Voeltz, Gia K.
(2012).
Organelle biogenesis and autophagy.
Molecular Biology of the Cell.
ISSN 1059-1524.
23(6),
s. 981–981.
doi:
10.1091/mbc.E11-12-0979.
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Søreng, Kristiane & Simonsen, Anne
(2017).
Regulation of autophagosome formation by the PX-domain proteins SNX18 and HS1BP3.
Universitetet i Oslo.
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Holland, Petter & Simonsen, Anne
(2016).
Novel proteins involved in lysosomal trafficking and degradation through autophagy.
Universitetet i Oslo.
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Publisert
13. apr. 2011 10:40
- Sist endret
2. juli 2020 12:51