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Linear ubiquitination controls Salmonella growth

08. May 2017

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A team around Ivan Dikic and Mike Heilemann (Chemistry Department, Goethe University) gained unprecedented insight into the mechanism by which cells fight Salmonella infections. Upon intracellular invasion, bacteria are usually rapidly surrounded by a coat of ubiquitin, the function of which remained unclear until now. Combining super-resolution microscopy with cell biological analysis, the researchers now discovered that distinct ubiquitin chains transform the bacterial surface into a molecular signalling platform. They were able to visualize the nanoscale distribution of different ubiquitin chains on the bacterial surface. One chain type, so called linear chains, specifically triggers pro-inflammatory signalling cascades, thereby restricting bacterial proliferation. In addition, the researchers identified the deubiquitinase OTULIN as a regulator capable of limiting this reaction – a very important notion considering the fact that excessive inflammation is one of the major causes of tissue damage following bacterial infection. In collaboration with colleagues from Japan, the Frankfurt researchers now published their results in the latest online issue of Nature Microbiology. Their work is an excellent example for interdisciplinary collaboration and was enabled by funding of several large research networks, e.g. the Cluster of Excellence Macromolecular Complexes, the CRC 1177 on selective autophagy and the LOEWE ubiquitin network. The discovery paves the way for many new projects. Very recently, Ivan Dikic obtained one of the prestigious ERC Advanced Grants in which he will investigate the role of ubiquitin in modulating the host-pathogen interaction in more detail. 






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Registration still open: 30th ENCP Congress, September 2nd - 5th, 2017, Paris, France

07. Feb 2017

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Symposium on Neuronal Autophagy 

SFB 1177 vice speaker Christian Behl will be chairing the symposium „Neuronal autophagy: Concepts and treatment options“ at the 30th ENCP Congress (September 2nd - 5th, 2017, Paris, France). 






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Fluorescence-based sensors for specifically monitoring autophagy

06. Feb 2017

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Autophagy is a cellular recycling and quality control pathway that is essential for maintaining cellular metabolism and homeostasis. Its malfunction contributes e.g. to neurodegenerative diseases and cancer.
Ubiquitin-like ATG8 proteins constitute central components of the autophagic machinery. However, until today, it is not completely clear why yeast harbors only one ATG8 protein while human cells contain six mammalian ATG8 orthologs, classified into the LC3 and GABARAP subfamilies. Using an interdisciplinary approach combining phage display with additional functional biochemical assays as well as cellular biology, the laboratories of Ivan Dikic and Andreas Ernst now engineered a valuable tool for studying specific functions of LC3 and GABARAP proteins. They developed fluorescence-based sensors that are able to discriminate between the six different members of the mammalian ATG8 protein family and track their actions within cells. As first application, the scientists successfully monitored the involvement of LC3C in selective autophagy of mitochondria (mitophagy) and Salmonella (xenophagy). The joint effort of the Dikic and Ernst groups has been published recently in EMBO Journal and will be helpful in decoding biological functions of individual LC3/GABARAP proteins. 






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How Salmonella tricks the immune system.

13. Jan 2017

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Infections with bacterial pathogens represent a global burden and are a major cause of death worldwide. For the design of new treatment paradigms it is essential to understand the intricate interplay between bacterial virulence strategies and host defense. The Dikic laboratory now added the next piece to the puzzle: They elucidated how the Salmonella effector enzyme SopA, a HECT-like E3 ligase, targets two host proteins involved in activating the immune defense (TRIM56 and TRIM65) and triggers their degradation. Atomic details of this new mechanism have now been published in Nature Communications and give a detailed insight into how Salmonella increases its own infectivity by interfering with the host immune response.






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Autophagy captures the Nobel Prize.

10. Dec 2016

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This year’s Nobel Essay in Cell has been written by Ivan Dikic (IBC2) together with Sharon Tooze (Francis Crick Institute, London). Published on time for the Nobel Ceremony on 10th December, the article highlights milestones leading to the discovery of the molecular principles underlying autophagy by Yoshinori Ohsumi, who is this years’ winner of the Nobel Prize for Medicine or Physiology. Dikic and Tooze tell the story of a simple yet insightful yeast genetic screen that revealed what later was recognized to be one of the most powerful quality-control pathways in cells.






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New ubiquitin chemistry regulates life processes

01. Dec 2016

Image: news/01.12.16-pub-1-.png Image: news/picture1-1-.png

In the latest issue of Cell, a team around IBC2 director and SFB 1177 speaker Ivan Dikic reveals molecular details of a novel ubiquitination mechanism that may affect numerous life processes. Earlier this year, U.S. colleagues reported that Legionella enzyme SdeA is capable of catalysing ubiquitination single-handedly. Now, the Frankfurt scientists together with collaborators from the MPI for Biology of Ageing (Cologne) have elucidated the chemistry behind and discovered a hitherto unknown type of linkage between ubiquitin and target proteins. Unlike the conventional ubiquitination reaction, the novel one is NAD-dependent, involving an ADP-ribose intermediate and resulting in the attachment of ubiquitin to substrate serine residues via a phosphodiester bond.
While those findings alone are breaking new ground, the discovery went even further: The team showed that the Legionella enzyme does not only transfer ubiquitin onto target proteins, but also leaves behind a complete pool of chemically modified, phosphoribosylated ubiquitin. Phosphoribosylated ubiquitin almost completely inhibits the conventional ubiquitination system and thereby affects essential cellular processes, e.g. proteasomal protein degradation, mitophagy and pro-inflammatory signalling. This explains the pathogenic effects of Legionella infection in immunocompromised patients, who often suffer from extensive lung tissue damage despite antibiotic treatment. The insight generated by the Dikic team may now open the road to the development of new antibacterial agents, which could complement conventional antibiotics by limiting the cellular damage induced by bacterial enzymes. 






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2019

Chaikuad A, Koschade SE, Stolz A, Zivkovic K, Pohl C, Shaid S, Ren H, Lambert LJ, Cosford NDP, Brandts CH & Knapp S. 2019. Conservation of structure, function and inhibitor binding in UNC-51-like kinase 1 and 2 (ULK1/2). Biochem J, 476, 875-887.

Chakraborty D, Felzen V, Hiebel C, Stuerner E, Perumal N, Manicam C, Grus F, Wolfrum U, Behl C. 2019. Enhanced autophagic-lysosomal activity and increased BAG3-mediated selective macroautophagy as adaptive response of neuronal cells to chronic oxidative stress. Redox Biol, accepted

Christ MG, Huesmann H, Nagel H, Kern A & Behl C. 2019. Sigma-1 receptor activation induces autophagy and increases proteostasis capacity in vitro and in vivo. Cells, 8, pii: E211

Forrester A, De Leonibus C, Grumati P, Fasana E, Piemontese M, Staiano L, Fregno I, Raimondi A, Marazza A, Bruno G, Iavazzo M, Intartaglia D, Seczynska M, van Anken E, Conte I, De Matteis MA, Dikic I, Molinari M, Settembre C. 2019. A selective ER-phagy exerts procollagen quality control via a Calnexin- FAM134B complex. EMBO J, 38, pii:299847

Fottner M, Brunner AD, Bittl V, Horn-Ghetko, Jussupow A, Kaila VRI, Bremm A & Lang K. 2019. Sitespecific ubiquitylation and SUMOylation

Huber J, Obata M, Gruber J, Akutsu M, Löhr F, Rogova N, Guentert P, Dikic I, Kirkin V, Komatsu M, Dötsch V, Rogov VV. 2019. An atypical LIR motif within UFM1-activating enzyme 5 (UBA5) reveals an alternative function for GABARAP proteins. Autophagy, accepted.

Juretschke T, Beli P & Dikic I. 2019. Quantitative phosphoproteomics of selective autophagy receptors. pages 691–701, In: Autophagy; Methods in Molecular Biology. Vol. 1880 (eds. Ktistakis N and Florey O). Humana Press, New York.

Key J, Mueller AK, Gispert S, Matschke L, Wittig I, Corti O, Muench C, Decher N, Auburger G. 2019. Ubiquitylome profiling of Parkin-null brain reveals dysregulation of calcium homeostasis factors ATP1A2, Hippocalcin and GNA11, reflected by altered firing of noradrenergic neurons. Neurobiol Dis, 127, 114- 130.

Lim R, Sugino T, Nolte H, Andrade J, Zimmermann B, Shi C, Doddaballapur A, Ong YT, Wilhelm K, Fasse JWD, Ernst A, Kaulich M, Husnjak K, Boettger T, Guenther S, Braun T, Krueger M, Benedito R, Dikic I. Potente M. 2019. Deubiquitinase USP10 regulates Notch signaling in the endothelium. Science, 364, 188-193.

Nguyen TD, Shaid S, Vakhrusheva O, Koschade SE, Klann K, Thölken M, Baker F, Zhang J, Oellerich T, Sürün D, Derlet A, Haberbosch I, Eimer S, Osiewacz HD, Behrends C, Münch C, Dikic I, Brandts CH. 2019. Loss of the selective autophagy receptor p62 impairs murine myeloid leukemia progression and mitophagy. Blood, 133, 168-179.

Poluzzi C, Nastase MV, Zeng-Brouwers J, Roedig H, Hsieh LTH, Michaelis JB, Buhl EM, Rezende F, Manavski Y, Bleich A, Boor P, Brandes RP, Pfeilschifter J, Stelzer EHK, Muench C, Dikic I, Brandts C, Iozzo RV, Wygrecka M & Schaefer L. 2019. Biglycan evokes autophagy in macrophages via a novel CD44/Toll-like receptor 4 signaling axis: Impact on renal ischemia/reperfusion injury. Kidney Int, 95, 540- 562

Roedig H, Nastase MV, Wygrecka M & Schaefer L. 2019. Breaking down chronic inflammatory diseases: the role of biglycan in promoting a switch between inflammation and autophagy. FEBS J, doi: 10.1111/febs.14791

Van Well EM, Bader V, Patra M, Sánchez-Vicente A, Meschede J, Furthmann N, Schnack C, Blusch A, Longworth J, Petrasch-Parwez E, Mori K, Arzberger, Trümbach D, Angersbach L, Showkat C, Sehr DA, Berlemann LA, Goldmann P, Clement AM, Behl C, Woerner AC, Saft C, Wurst W, Haass C, Ellrichmann G, Gold R, Dittmar G, Hipp MS, Hartl FU, Tatzelt J, Winklhofer KF. 2019. A protein quality control pathway regulated by linear ubiquitination. EMBO J, pii: e100730.

Wegner M, Diehl V, Bittl V, de Bruyn R, Wiechmann S, Matthess Y, Hebel M, Hayes MG, Schaubeck S, Benner C, Heinz S, Bremm A, Dikic I, Ernst A, Kaulich M. 2019. Circular synthesized CRISPR/Cas gRNAs for functional interrogations in the coding and noncoding genome. eLife, 8, pii: e42549.

2018

Di Rita A, Peschiaroli A, D Acunzo P, Strobbe D, Hu Z, Gruber J, Nygaard M, Lambrughi M, Melino G, Papaleo E, Dengjel J, El Alaoui S, Campanella M, Dötsch V, Rogov VV, Strappazzon F, Cecconi F. HUWE1 E3 ligase promotes PINK1/PARKIN-independent mitophagy by regulating AMBRA1 activation via IKKα. Nat Commun. 2018 Sep 14;9(1):3755. doi: 10.1038/s41467-018-05722-3. PubMed PMID: 30217973; PubMed Central PMCID: PMC6138665.

Kniss A, Kazemi S, Löhr F, Berger M, Rogov VV, Güntert P, Sommer T, Jarosch E, Dötsch V. Structural investigation of glycan recognition by the ERAD quality control lectin Yos9. J Biomol NMR. 2018 Jul 31. doi: 10.1007/s10858-018-0201-6. [Epub ahead of print] PubMed PMID: 30066206.

Meyer N, Zielke S, Michaelis JB, Linder B, Warnsmann V, Rakel S, Osiewacz HD, Fulda S, Mittelbronn M, Münch C, Behrends C, Kögel D. AT 101 induces early mitochondrial dysfunction and HMOX1 (heme oxygenase 1) to trigger mitophagic cell death in glioma cells. Autophagy. 2018;14(10):1693-1709. doi: 10.1080/15548627.2018.1476812. Epub 2018 Jul 21. PubMed PMID: 29938581; PubMed Central PMCID: PMC6135628.

Phelan JD, Young RM, Webster DE, Roulland S, Wright GW, Kasbekar M, Shaffer AL 3rd, Ceribelli M, Wang JQ, Schmitz R, Nakagawa M, Bachy E, Huang DW, Ji Y, Chen L, Yang Y, Zhao H, Yu X, Xu W, Palisoc MM, Valadez RR, Davies-Hill T, Wilson WH, Chan WC, Jaffe ES, Gascoyne RD, Campo E, Rosenwald A, Ott G, Delabie J, Rimsza LM, Rodriguez FJ, Estephan F, Holdhoff M, Kruhlak MJ, Hewitt SM, Thomas CJ, Pittaluga S, Oellerich T, Staudt LM. A multiprotein supercomplex controlling oncogenic signalling in lymphoma. Nature. 2018 Aug;560(7718):387-391. doi: 10.1038/s41586-018-0290-0. Epub 2018 Jun 20. PubMed PMID: 29925955.

Ziegler PK, Bollrath J, Pallangyo CK, Matsutani T, Canli Ö, De Oliveira T, Diamanti MA, Müller N, Gamrekelashvili J, Putoczki T, Horst D, Mankan AK, Öner MG, Müller S, Müller-Höcker J, Kirchner T, Slotta-Huspenina J, Taketo MM, Reinheckel T, Dröse S, Larner AC, Wels WS, Ernst M, Greten TF, Arkan MC, Korn T, Wirth D, Greten FR. Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis. Cell. 2018 Jun 28;174(1):88-101.e16. doi: 10.1016/j.cell.2018.05.028. Epub 2018 Jun 14. PubMed PMID: 29909986.

Kern A, Spang N, Huesmann H, Behl C. Novel Modulators of Proteostasis: RNAi Screen of Chromosome I in a Heat Stress Paradigm in C. elegans. Cells. 2018 May 26;7(6). pii: E49. doi: 10.3390/cells7060049. PubMed PMID: 29861461; PubMed Central PMCID: PMC6025327.

Roedig H, Nastase MV, Frey H, Moreth K, Zeng-Brouwers J, Poluzzi C, Hsieh LT, Brandts C, Fulda S, Wygrecka M, Schaefer L. Biglycan is a new high-affinity ligand for CD14 in macrophages. Matrix Biol. 2018 May 17. pii: S0945-053X(18)30186-0. doi: 10.1016/j.matbio.2018.05.006. [Epub ahead of print] PubMed PMID: 29777767.

Harwardt MIE, Dietz MS, Heilemann M, Wohland T. SPT and Imaging FCS Provide Complementary Information on the Dynamics of Plasma Membrane Molecules. Biophys J. 2018 May 22;114(10):2432-2443. doi: 10.1016/j.bpj.2018.03.013. Epub 2018 Apr 9. PubMed PMID: 29650369; PubMed Central PMCID: PMC6129459.

Dikic I, Elazar Z. Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol. 2018 Jun;19(6):349-364. doi: 10.1038/s41580-018-0003-4. Review. PubMed PMID: 29618831.

Kunz K, Piller T, Müller S. SUMO-specific proteases and isopeptidases of the SENP family at a glance. J Cell Sci. 2018 Mar 20;131(6). pii: jcs211904. doi: 10.1242/jcs.211904. Review. PubMed PMID: 29559551.

Fulda S. Targeting autophagy for the treatment of cancer. Biol Chem. 2018 Jun 27;399(7):673-677. doi: 10.1515/hsz-2018-0105. PubMed PMID: 29500917.

Heidelberger JB, Voigt A, Borisova ME, Petrosino G, Ruf S, Wagner SA, Beli P. Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function. EMBO Rep. 2018 Apr;19(4). pii: e44754. doi: 10.15252/embr.201744754. Epub 2018 Feb 21. PubMed PMID: 29467282; PubMed Central PMCID: PMC5891417.

Das CK, Linder B, Bonn F, Rothweiler F, Dikic I, Michaelis M, Cinatl J, Mandal M, Kögel D. BAG3 Overexpression and Cytoprotective Autophagy Mediate Apoptosis Resistance in Chemoresistant Breast Cancer Cells. Neoplasia. 2018 Mar;20(3):263-279. doi: 10.1016/j.neo.2018.01.001. Epub 2018 Feb 22. PubMed PMID: 29462756; PubMed Central PMCID: PMC5852393.

Kniss A, Schuetz D, Kazemi S, Pluska L, Spindler PE, Rogov VV, Husnjak K, Dikic I, Güntert P, Sommer T, Prisner TF, Dötsch V. Chain Assembly and Disassembly Processes Differently Affect the Conformational Space of Ubiquitin Chains. Structure. 2018 Feb 6;26(2):249-258.e4. doi: 10.1016/j.str.2017.12.011. Epub 2018 Jan 18. PubMed PMID: 29358025.

Carmona-Gutierrez D, Bauer MA, Zimmermann A, Aguilera A, Austriaco N, Ayscough K, Balzan R, Bar-Nun S, Barrientos A, Belenky P, Blondel M, Braun RJ, Breitenbach M, Burhans WC, Büttner S, Cavalieri D, Chang M, Cooper KF, Côrte-Real M, Costa V, Cullin C, Dawes I, Dengjel J, Dickman MB, Eisenberg T, Fahrenkrog B, Fasel N, Fröhlich KU, Gargouri A, Giannattasio S, Goffrini P, Gourlay CW, Grant CM, Greenwood MT, Guaragnella N, Heger T, Heinisch J, Herker E, Herrmann JM, Hofer S, Jiménez-Ruiz A, Jungwirth H, Kainz K, Kontoyiannis DP, Ludovico P, Manon S, Martegani E, Mazzoni C, Megeney LA, Meisinger C, Nielsen J, Nyström T, Osiewacz HD, Outeiro TF, Park HO, Pendl T, Petranovic D, Picot S, Polčic P, Powers T, Ramsdale M, Rinnerthaler M, Rockenfeller P, Ruckenstuhl C, Schaffrath R, Segovia M, Severin FF, Sharon A, Sigrist SJ, Sommer-Ruck C, Sousa MJ, Thevelein JM, Thevissen K, Titorenko V, Toledano MB, Tuite M, Vögtle FN, Westermann B, Winderickx J, Wissing S, Wölfl S, Zhang ZJ, Zhao RY, Zhou B, Galluzzi L, Kroemer G, Madeo F. Guidelines and recommendations on yeast cell death nomenclature. Microb Cell. 2018 Jan 1;5(1):4-31. doi: 10.15698/mic2018.01.607. Review. PubMed PMID: 29354647; PubMed Central PMCID: PMC5772036.

Frevert CW, Felgenhauer J, Wygrecka M, Nastase MV, Schaefer L. Danger-Associated Molecular Patterns Derived From the Extracellular Matrix Provide Temporal Control of Innate Immunity. J Histochem Cytochem. 2018 Apr;66(4):213-227. doi: 10.1369/0022155417740880. Epub 2018 Jan 1. PubMed PMID: 29290139; PubMed Central PMCID: PMC5958376.

Nastase MV, Janicova A, Roedig H, Hsieh LT, Wygrecka M, Schaefer L. Small Leucine-Rich Proteoglycans in Renal Inflammation: Two Sides of the Coin. J Histochem Cytochem. 2018 Apr;66(4):261-272. doi: 10.1369/0022155417738752. Epub 2018 Jan 1. PubMed PMID: 29290137; PubMed Central PMCID: PMC5958374.

2017

Nastase MV, Zeng-Brouwers J, Wygrecka M, Schaefer L. Targeting renal fibrosis: Mechanisms and drug delivery systems. Adv Drug Deliv Rev. 2018 Apr;129:295-307. doi: 10.1016/j.addr.2017.12.019. Epub 2017 Dec 27. Review. PubMed PMID: 29288033.

Nastase MV, Zeng-Brouwers J, Beckmann J, Tredup C, Christen U, Radeke HH, Wygrecka M, Schaefer L. Biglycan, a novel trigger of Th1 and Th17 cell recruitment into the kidney. Matrix Biol. 2018 Aug;68-69:293-317. doi: 10.1016/j.matbio.2017.12.002. Epub 2017 Dec 15. PubMed PMID: 29253517.

Grumati P, Dikic I. Ubiquitin signaling and autophagy. J Biol Chem. 2018 Apr 13;293(15):5404-5413. doi: 10.1074/jbc.TM117.000117. Epub 2017 Nov 29. Review. PubMed PMID: 29187595; PubMed Central PMCID: PMC5900779.

Le Guerroué F, Eck F, Jung J, Starzetz T, Mittelbronn M, Kaulich M, Behrends C. Autophagosomal Content Profiling Reveals an LC3C-Dependent Piecemeal Mitophagy Pathway. Mol Cell. 2017 Nov 16;68(4):786-796.e6. doi: 10.1016/j.molcel.2017.10.029. PubMed PMID: 29149599.

Jung J, Behrends C. Protocol for Establishing a Multiplex Image-based Autophagy RNAi Screen in Cell Cultures. Bio Protoc. 2017 Sep 5;7(17):27982478. doi: 10.21769/BioProtoc.2540. PubMed PMID: 28966949; PubMed Central PMCID: PMC5619641.

Varga J, Greten FR. Cell plasticity in epithelial homeostasis and tumorigenesis. Nat Cell Biol. 2017 Oct;19(10):1133-1141. doi: 10.1038/ncb3611. Epub 2017 Sep 25. Review. PubMed PMID: 28945230.

Harwardt MIE, Young P, Bleymüller WM, Meyer T, Karathanasis C, Niemann HH, Heilemann M, Dietz MS. Membrane dynamics of resting and internalin B-bound MET receptor tyrosine kinase studied by single-molecule tracking. FEBS Open Bio. 2017 Aug 29;7(9):1422-1440. doi: 10.1002/2211-5463.12285. eCollection 2017 Sep. PubMed PMID: 28904870; PubMed Central PMCID: PMC5586345.

Henkel V, Warnsmann V, Osiewacz HD. Autophagic responses compensate mitochondrial impairments. Aging (Albany NY). 2017 Sep 12;9(9):1947-1948. doi: 10.18632/aging.101292. PubMed PMID: 28904241; PubMed Central PMCID: PMC5636663.

Aguilera-Gomez A, Zacharogianni M, van Oorschot MM, Genau H, Grond R, Veenendaal T, Sinsimer KS, Gavis EA, Behrends C, Rabouille C. Phospho-Rasputin Stabilization by Sec16 Is Required for Stress Granule Formation upon Amino Acid Starvation. Cell Rep. 2017 Aug 29;20(9):2277. doi: 10.1016/j.celrep.2017.08.054. PubMed PMID: 28854374.

Schwalm S, Beyer S, Frey H, Haceni R, Grammatikos G, Thomas D, Geisslinger G, Schaefer L, Huwiler A, Pfeilschifter J. Sphingosine Kinase-2 Deficiency Ameliorates Kidney Fibrosis by Up-Regulating Smad7 in a Mouse Model of Unilateral Ureteral Obstruction. Am J Pathol. 2017 Nov;187(11):2413-2429. doi: 10.1016/j.ajpath.2017.06.017. Epub 2017 Aug 12. PubMed PMID: 28807595.

Reilly R, Mroz MS, Dempsey E, Wynne K, Keely SJ, McKone EF, Hiebel C, Behl C, Coppinger JA. Targeting the PI3K/Akt/mTOR signalling pathway in Cystic Fibrosis. Sci Rep. 2017 Aug 9;7(1):7642. doi: 10.1038/s41598-017-06588-z. PubMed PMID: 28794469; PubMed Central PMCID: PMC5550428.

Wiechmann S, Gärtner A, Kniss A, Stengl A, Behrends C, Rogov VV, Rodriguez MS, Dötsch V, Müller S, Ernst A. Site-specific inhibition of the small ubiquitin-like modifier (SUMO)-conjugating enzyme Ubc9 selectively impairs SUMO chain formation. J Biol Chem. 2017 Sep 15;292(37):15340-15351. doi: 10.1074/jbc.M117.794255. Epub 2017 Aug 7. PubMed PMID: 28784659; PubMed Central PMCID: PMC5602394.

Polajnar M, Dietz MS, Heilemann M, Behrends C. Expanding the host cell ubiquitylation machinery targeting cytosolic Salmonella. EMBO Rep. 2017 Sep;18(9):1572-1585. doi: 10.15252/embr.201643851. Epub 2017 Aug 6. PubMed PMID: 28784601; PubMed Central PMCID: PMC5579355.

Jung J, Behrends C. Multifaceted role of SMCR8 as autophagy regulator. Small GTPases. 2017 Jul 11:1-9. doi: 10.1080/21541248.2017.1346553. [Epub ahead of print] PubMed PMID: 28696821.

Warnsmann V, Meyer N, Hamann A, Kögel D, Osiewacz HD. A novel role of the mitochondrial permeability transition pore in (-)-gossypol-induced mitochondrial dysfunction. Mech Ageing Dev. 2018 Mar;170:45-58. doi: 10.1016/j.mad.2017.06.004. Epub 2017 Jul 3. PubMed PMID: 28684269.

Stürner E, Behl C. The Role of the Multifunctional BAG3 Protein in Cellular Protein Quality Control and in Disease. Front Mol Neurosci. 2017 Jun 21;10:177. doi: 10.3389/fnmol.2017.00177. eCollection 2017. Review. PubMed PMID: 28680391; PubMed Central PMCID: PMC5478690.

Rogov VV, Stolz A, Ravichandran AC, Rios-Szwed DO, Suzuki H, Kniss A, Löhr F, Wakatsuki S, Dötsch V, Dikic I, Dobson RC, McEwan DG. Structural and functional analysis of the GABARAP interaction motif (GIM). EMBO Rep. 2017 Aug;18(8):1382-1396. doi: 10.15252/embr.201643587. Epub 2017 Jun 27. PubMed PMID: 28655748; PubMed Central PMCID: PMC5538626.

Grumati P, Morozzi G, Hölper S, Mari M, Harwardt MI, Yan R, Müller S, Reggiori F, Heilemann M, Dikic I. Full length RTN3 regulates turnover of tubular endoplasmic reticulum via selective autophagy. Elife. 2017 Jun 15;6. pii: e25555. doi: 10.7554/eLife.25555. PubMed PMID: 28617241; PubMed Central PMCID: PMC5517149.

Galluzzi L, Baehrecke EH, Ballabio A, Boya P, Bravo-San Pedro JM, Cecconi F, Choi AM, Chu CT, Codogno P, Colombo MI, Cuervo AM, Debnath J, Deretic V, Dikic I, Eskelinen EL, Fimia GM, Fulda S, Gewirtz DA, Green DR, Hansen M, Harper JW, Jäättelä M, Johansen T, Juhasz G, Kimmelman AC, Kraft C, Ktistakis NT, Kumar S, Levine B, Lopez-Otin C, Madeo F, Martens S, Martinez J, Melendez A, Mizushima N, Münz C, Murphy LO, Penninger JM, Piacentini M, Reggiori F, Rubinsztein DC, Ryan KM, Santambrogio L, Scorrano L, Simon AK, Simon HU, Simonsen A, Tavernarakis N, Tooze SA, Yoshimori T, Yuan J, Yue Z, Zhong Q, Kroemer G. Molecular definitions of autophagy and related processes. EMBO J. 2017 Jul 3;36(13):1811-1836. doi: 10.15252/embj.201796697. Epub 2017 Jun 8. Review. PubMed PMID: 28596378; PubMed Central PMCID: PMC5494474.

Nastase MV, Janicova A, Wygrecka M, Schaefer L. Signaling at the Crossroads: Matrix-Derived Proteoglycan and Reactive Oxygen Species Signaling. Antioxid Redox Signal. 2017 Oct 20;27(12):855-873. doi: 10.1089/ars.2017.7165. Epub 2017 Jul 5. Review. PubMed PMID: 28510506.

van Wijk SJL, Fricke F, Herhaus L, Gupta J, Hötte K, Pampaloni F, Grumati P, Kaulich M, Sou YS, Komatsu M, Greten FR, Fulda S, Heilemann M, Dikic I. Linear ubiquitination of cytosolic Salmonella Typhimurium activates NF-κB and restricts bacterial proliferation. Nat Microbiol. 2017 May 8;2:17066. doi: 10.1038/nmicrobiol.2017.66. PubMed PMID: 28481361. Dikic I. Proteasomal and Autophagic Degradation Systems. Annu Rev Biochem. 2017 Jun 20;86:193-224. doi: 10.1146/annurev-biochem-061516-044908. Epub 2017 May 1. Review. PubMed PMID: 28460188.

Knuppertz L, Osiewacz HD. Autophagy compensates impaired energy metabolism in CLPXP-deficient Podospora anserina strains and extends healthspan. Aging Cell. 2017 Aug;16(4):704-715. doi: 10.1111/acel.12600. Epub 2017 Apr 27. PubMed PMID: 28449241; PubMed Central PMCID: PMC5506401.

Rogov VV, Suzuki H, Marinković M, Lang V, Kato R, Kawasaki M, Buljubašić M, Šprung M, Rogova N, Wakatsuki S, Hamacher-Brady A, Dötsch V, Dikic I, Brady NR, Novak I. Phosphorylation of the mitochondrial autophagy receptor Nix enhances its interaction with LC3 proteins. Sci Rep. 2017 Apr 25;7(1):1131. doi: 10.1038/s41598-017-01258-6. PubMed PMID: 28442745; PubMed Central PMCID: PMC5430633.

Knuppertz L, Warnsmann V, Hamann A, Grimm C, Osiewacz HD. Stress-dependent opposing roles for mitophagy in aging of the ascomycete Podospora anserina. Autophagy. 2017 Jun 3;13(6):1037-1052. doi: 10.1080/15548627.2017.1303021. Epub 2017 Apr 3. PubMed PMID: 28368682; PubMed Central PMCID: PMC5486364.

Philipp O, Hamann A, Osiewacz HD, Koch I. The autophagy interaction network of the aging model Podospora anserina. BMC Bioinformatics. 2017 Mar 27;18(1):196. doi: 10.1186/s12859-017-1603-2. PubMed PMID: 28347269; PubMed Central PMCID: PMC5369006.

Nayak A, Reck A, Morsczeck C, Müller S. Flightless-I governs cell fate by recruiting the SUMO isopeptidase SENP3 to distinct HOX genes. Epigenetics Chromatin. 2017 Mar 23;10:15. doi: 10.1186/s13072-017-0122-8. eCollection 2017. PubMed PMID: 28344658; PubMed Central PMCID: PMC5364561.

Feldmann A, Bekbulat F, Huesmann H, Ulbrich S, Tatzelt J, Behl C, Kern A. The RAB GTPase RAB18 modulates macroautophagy and proteostasis. Biochem Biophys Res Commun. 2017 May 6;486(3):738-743. doi: 10.1016/j.bbrc.2017.03.112. Epub 2017 Mar 22. PubMed PMID: 28342870.

Pampaloni F, Mayer B, Kabat Vel-Job K, Ansari N, Hötte K, Kögel D, Stelzer EHK. A Novel Cellular Spheroid-Based Autophagy Screen Applying Live Fluorescence Microscopy Identifies Nonactin as a Strong Inducer of Autophagosomal Turnover. SLAS Discov. 2017 Jun;22(5):558-570. doi: 10.1177/2472555217696798. Epub 2017 Mar 15. PubMed PMID: 28297606.

Hsieh LT, Nastase MV, Roedig H, Zeng-Brouwers J, Poluzzi C, Schwalm S, Fork C, Tredup C, Brandes RP, Wygrecka M, Huwiler A, Pfeilschifter J, Schaefer L. Biglycan- and Sphingosine Kinase-1 Signaling Crosstalk Regulates the Synthesis of Macrophage Chemoattractants. Int J Mol Sci. 2017 Mar 9;18(3). pii: E595. doi: 10.3390/ijms18030595. PubMed PMID: 28282921; PubMed Central PMCID: PMC5372611.

Johansen T, Birgisdottir ÅB, Huber J, Kniss A, Dötsch V, Kirkin V, Rogov VV. Methods for Studying Interactions Between Atg8/LC3/GABARAP and LIR-Containing Proteins. Methods Enzymol. 2017;587:143-169. doi: 10.1016/bs.mie.2016.10.023. Epub 2017 Jan 12. PubMed PMID: 28253953.

Jung J, Nayak A, Schaeffer V, Starzetz T, Kirsch AK, Müller S, Dikic I, Mittelbronn M, Behrends C. Multiplex image-based autophagy RNAi screening identifies SMCR8 as ULK1 kinase activity and gene expression regulator. Elife. 2017 Feb 14;6. pii: e23063. doi: 10.7554/eLife.23063. PubMed PMID: 28195531; PubMed Central PMCID: PMC5323046.

Fiskin E, Bhogaraju S, Herhaus L, Kalayil S, Hahn M, Dikic I. Structural basis for the recognition and degradation of host TRIM proteins by Salmonella effector SopA. Nat Commun. 2017 Jan 13;8:14004. doi: 10.1038/ncomms14004. PubMed PMID: 28084320; PubMed Central PMCID: PMC5241803.

Diamanti MA, Gupta J, Bennecke M, De Oliveira T, Ramakrishnan M, Braczynski AK, Richter B, Beli P, Hu Y, Saleh M, Mittelbronn M, Dikic I, Greten FR. IKKα controls ATG16L1 degradation to prevent ER stress during inflammation. J Exp Med. 2017 Feb;214(2):423-437. doi: 10.1084/jem.20161867. Epub 2017 Jan 12. PubMed PMID: 28082356; PubMed Central PMCID: PMC5294863.

Aglan A, Longen S, Dehne N, Köhler Y, Hassan M, Beck M, Tredup C, Boosen M, Hsieh TL, Schaefer L, Beck KF, Pfeilschifter J. Nitric oxide mediates prolyl hydroxylase 3 expression in mesangial cells and in glomerulonephritis. J Mol Med (Berl). 2017 Mar;95(3):257-271. doi: 10.1007/s00109-016-1503-3. Epub 2017 Jan 4. PubMed PMID: 28054119.

2016

Schönbühler B, Schmitt V, Huesmann H, Kern A, Gamerdinger M, Behl C. BAG2 Interferes with CHIP-Mediated Ubiquitination of HSP72. Int J Mol Sci. 2016 Dec 30;18(1). pii: E69. doi: 10.3390/ijms18010069. PubMed PMID: 28042827; PubMed Central PMCID: PMC5297704.

Stolz A, Putyrski M, Kutle I, Huber J, Wang C, Major V, Sidhu SS, Youle RJ, Rogov VV, Dötsch V, Ernst A, Dikic I. Fluorescence-based ATG8 sensors monitor localization and function of LC3/GABARAP proteins. EMBO J. 2017 Feb 15;36(4):549-564. doi: 10.15252/embj.201695063. Epub 2016 Dec 27. PubMed PMID: 28028054; PubMed Central PMCID: PMC5437816.

Bhogaraju S, Kalayil S, Liu Y, Bonn F, Colby T, Matic I, Dikic I. Phosphoribosylation of Ubiquitin Promotes Serine Ubiquitination and Impairs Conventional Ubiquitination. Cell. 2016 Dec 1;167(6):1636-1649.e13. doi: 10.1016/j.cell.2016.11.019. PubMed PMID: 27912065.

Schaefer L, Tredup C, Gubbiotti MA, Iozzo RV. Proteoglycan neofunctions: regulation of inflammation and autophagy in cancer biology. FEBS J. 2017 Jan;284(1):10-26. doi: 10.1111/febs.13963. Epub 2016 Dec 7. Review. PubMed PMID: 27860287; PubMed Central PMCID: PMC5226885.

Lopez-Mosqueda J, Maddi K, Prgomet S, Kalayil S, Marinovic-Terzic I, Terzic J, Dikic I. SPRTN is a mammalian DNA-binding metalloprotease that resolves DNA-protein crosslinks. Elife. 2016 Nov 17;5. pii: e21491. doi: 10.7554/eLife.21491. PubMed PMID: 27852435; PubMed Central PMCID: PMC5127644.

Hoeller D, Dikic I. How the proteasome is degraded. Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):13266-13268. Epub 2016 Nov 11. PubMed PMID: 27837026; PubMed Central PMCID: PMC5127301.

Beetz N, Rommel C, Schnick T, Neumann E, Lother A, Monroy-Ordonez EB, Zeeb M, Preissl S, Gilsbach R, Melchior-Becker A, Rylski B, Stoll M, Schaefer L, Beyersdorf F, Stiller B, Hein L. Ablation of biglycan attenuates cardiac hypertrophy and fibrosis after left ventricular pressure overload. J Mol Cell Cardiol. 2016 Dec;101:145-155. doi: 10.1016/j.yjmcc.2016.10.011. Epub 2016 Oct 24. PubMed PMID: 27789290.

Antonietti P, Linder B, Hehlgans S, Mildenberger IC, Burger MC, Fulda S, Steinbach JP, Gessler F, Rödel F, Mittelbronn M, Kögel D. Interference with the HSF1/HSP70/BAG3 Pathway Primes Glioma Cells to Matrix Detachment and BH3 Mimetic-Induced Apoptosis. Mol Cancer Ther. 2017 Jan;16(1):156-168. doi: 10.1158/1535-7163.MCT-16-0262. Epub 2016 Oct 24. PubMed PMID: 27777286.

Pesic M, Greten FR. Inflammation and cancer: tissue regeneration gone awry. Curr Opin Cell Biol. 2016 Dec;43:55-61. doi: 10.1016/j.ceb.2016.07.010. Epub 2016 Aug 10. Review. PubMed PMID: 27521599.

Kramer P, Jung AT, Hamann A, Osiewacz HD. Cyclophilin D Is Involved in the Regulation of Autophagy and Affects the Lifespan of P. anserina in Response to Mitochondrial Oxidative Stress. Front Genet. 2016 Sep 14;7:165. doi: 10.3389/fgene.2016.00165. eCollection 2016. PubMed PMID: 27683587; PubMed Central PMCID: PMC5021683.

Frey H, Moreth K, Hsieh LT, Zeng-Brouwers J, Rathkolb B, Fuchs H, Gailus-Durner V, Iozzo RV, de Angelis MH, Schaefer L. A novel biological function of soluble biglycan: Induction of erythropoietin production and polycythemia. Glycoconj J. 2017 Jun;34(3):393-404. doi: 10.1007/s10719-016-9722-y. Epub 2016 Sep 6. PubMed PMID: 27600268.

Weishaupt JH, Hyman T, Dikic I. Common Molecular Pathways in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Trends Mol Med. 2016 Sep;22(9):769-783. doi: 10.1016/j.molmed.2016.07.005. Epub 2016 Aug 4. Review. PubMed PMID: 27498188.

Fiskin E, Bionda T, Dikic I, Behrends C. Global Analysis of Host and Bacterial Ubiquitinome in Response to Salmonella Typhimurium Infection. Mol Cell. 2016 Jun 16;62(6):967-981. doi: 10.1016/j.molcel.2016.04.015. Epub 2016 May 19. PubMed PMID: 27211868.

Behl C. Breaking BAG: The Co-Chaperone BAG3 in Health and Disease. Trends Pharmacol Sci. 2016 Aug;37(8):672-688. doi: 10.1016/j.tips.2016.04.007. Epub 2016 May 6. Review. PubMed PMID: 27162137.

Richter B, Sliter DA, Herhaus L, Stolz A, Wang C, Beli P, Zaffagnini G, Wild P, Martens S, Wagner SA, Youle RJ, Dikic I. Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria. Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):4039-44. doi: 10.1073/pnas.1523926113. Epub 2016 Mar 30. PubMed PMID: 27035970; PubMed Central PMCID: PMC4839414.

Jennewein L, Ronellenfitsch MW, Antonietti P, Ilina EI, Jung J, Stadel D, Flohr LM, Zinke J, von Renesse J, Drott U, Baumgarten P, Braczynski AK, Penski C, Burger MC, Theurillat JP, Steinbach JP, Plate KH, Dikic I, Fulda S, Brandts C, Kögel D, Behrends C, Harter PN, Mittelbronn M. Diagnostic and clinical relevance of the autophago-lysosomal network in human gliomas. Oncotarget. 2016 Apr 12;7(15):20016-32. doi: 10.18632/oncotarget.7910. PubMed PMID: 26956048; PubMed Central PMCID: PMC4991435.

Habisov S, Huber J, Ichimura Y, Akutsu M, Rogova N, Loehr F, McEwan DG, Johansen T, Dikic I, Doetsch V, Komatsu M, Rogov VV, Kirkin V. Structural and Functional Analysis of a Novel Interaction Motif within UFM1-activating Enzyme 5 (UBA5) Required for Binding to Ubiquitin-like Proteins and Ufmylation. J Biol Chem. 2016 Apr 22;291(17):9025-41. doi: 10.1074/jbc.M116.715474. Epub 2016 Feb 29. PubMed PMID: 26929408; PubMed Central PMCID: PMC4861472.

Rajalingam K, Dikic I. SnapShot: Expanding the Ubiquitin Code. Cell. 2016 Feb 25;164(5):1074-1074.e1. doi: 10.1016/j.cell.2016.02.019. PubMed PMID: 26919436.

Akutsu M, Dikic I, Bremm A. Ubiquitin chain diversity at a glance. J Cell Sci. 2016 Mar 1;129(5):875-80. doi: 10.1242/jcs.183954. Epub 2016 Feb 15. Review. PubMed PMID: 26906419.

Knuppertz L, Osiewacz HD. Orchestrating the network of molecular pathways affecting aging: Role of nonselective autophagy and mitophagy. Mech Ageing Dev. 2016 Jan;153:30-40. doi: 10.1016/j.mad.2016.01.003. Epub 2016 Jan 24. Review. PubMed PMID: 26814678.

Klionsky DJ, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016;12(1):1-222. doi: 0.1080/15548627.2015.1100356. Erratum in: Autophagy. 2016;12(2):443. Selliez, Iban [corrected to Seiliez, Iban]. PubMed PMID: 26799652; PubMed Central PMCID: PMC4835977.

Philipp O, Osiewacz HD, Koch I. Path2PPI: an R package to predict protein-protein interaction networks for a set of proteins. Bioinformatics. 2016 May 1;32(9):1427-9. doi: 10.1093/bioinformatics/btv765. Epub 2016 Jan 5. PubMed PMID: 26733452; PubMed Central PMCID: PMC4848400.

Antonietti P, Gessler F, Düssmann H, Reimertz C, Mittelbronn M, Prehn JH, Kögel D. AT-101 simultaneously triggers apoptosis and a cytoprotective type of autophagy irrespective of expression levels and the subcellular localization of Bcl-xL and Bcl-2 in MCF7 cells. Biochim Biophys Acta. 2016 Apr;1863(4):499-509. doi: 10.1016/j.bbamcr.2015.12.016. Epub 2015 Dec 22. PubMed PMID: 26721623.

Hsieh LT, Frey H, Nastase MV, Tredup C, Hoffmann A, Poluzzi C, Zeng-Brouwers J, Manon-Jensen T, Schröder K, Brandes RP, Iozzo RV, Schaefer L. Bimodal role of NADPH oxidases in the regulation of biglycan-triggered IL-1β synthesis. Matrix Biol. 2016 Jan;49:61-81. doi: 10.1016/j.matbio.2015.12.005. Epub 2015 Dec 12. PubMed PMID: 26689330.

uni-frankfurt.de Georg Speyer Haus Institut für Molekulare Biologie Johannes Gutenberg-Universität Mainz