TY - GEN AU - Mamar, Hasan AU - Fajka-Boja, Roberta AU - Mórocz, Mónika AU - Pinto, Eva AU - Siham, Zentout AU - Mihut, Alexandra AU - Kopasz, Anna Georgina AU - Mérey, Mihály AU - Rebecca, Smith AU - Haracska, Lajos AU - Sébastien, Huet AU - Timinszky, Gyula TI - The loss of DNA polymerase epsilon accessory subunits POLE3-POLE4 leads to BRCA1-independent PARP inhibitor sensitivity PY - 2023 UR - https://m2.mtmt.hu/api/publication/34169536 ID - 34169536 LA - English DB - MTMT ER - TY - JOUR AU - Longarini, E.J. AU - Dauben, H. AU - Locatelli, C. AU - Wondisford, A.R. AU - Smith, R. AU - Muench, C. AU - Kolvenbach, A. AU - Lynskey, M.L. AU - Pope, A. AU - Bonfiglio, J.J. AU - Jurado, E.P. AU - Fajka-Boja, Roberta AU - Colby, T. AU - Schuller, M. AU - Ahel, I. AU - Timinszky, Gyula AU - O'Sullivan, R.J. AU - Huet, S. AU - Matic, I. TI - Modular antibodies reveal DNA damage-induced mono-ADP-ribosylation as a second wave of PARP1 signaling JF - MOLECULAR CELL J2 - MOL CELL VL - 83 PY - 2023 IS - 10 SP - 1743 EP - 1760.e11 PG - 19 SN - 1097-2765 DO - 10.1016/j.molcel.2023.03.027 UR - https://m2.mtmt.hu/api/publication/34002643 ID - 34002643 N1 - Research Group of Proteomics and ADP-Ribosylation Signaling, Max Planck Institute for Biology of Ageing, Cologne, 50931, Germany Department of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, United States Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes) – UMR 6290, BIOSIT (Biologie, Santé, Innovation Technologique de Rennes) – UMS 3480, US 018, Rennes, 35000, France Laboratory of DNA Damage and Nuclear Dynamics, Institute of Genetics, Biological Research Centre, Eötvös Loránd Research Network (ELKH), Szeged, 6276, Hungary Doctoral School of Multidisciplinary Medical Sciences, University of Szeged, Szeged, 6276, Hungary Department of Immunology, Albert Szent-Györgyi Medical School, Faculty of Science and Informatics, University of Szeged, Szeged, 6720, Hungary Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, United Kingdom Institut Universitaire de France, Paris, France Cologne Excellence Cluster for Stress Responses in Ageing-Associated Diseases (CECAD), University of Cologne, Cologne, 50931, Germany Cited By :1 Export Date: 7 June 2023 CODEN: MOCEF Correspondence Address: Huet, S.; Univ Rennes, US 018, France; email: sebastien.huet@univ-rennes.fr Correspondence Address: Matic, I.; Research Group of Proteomics and ADP-Ribosylation Signaling, Germany; email: imatic@age.mpg.de Chemicals/CAS: histone, 9062-68-4; Antibodies; Chromatin; Histones; Poly (ADP-Ribose) Polymerase-1 Funding details: 657501, EXC229 Funding details: National Cancer Institute, NCI, R01CA207209, R01CA262316 Funding details: Wellcome Trust, WT, 101794, 210634 Funding details: Ovarian Cancer Research Alliance, OCRA, 813369 Funding details: Biotechnology and Biological Sciences Research Council, BBSRC, BB/R007195/1 Funding details: Cancer Research UK, CRUK, C35050/A22284 Funding details: European Research Council, ERC Funding details: Deutsche Forschungsgemeinschaft, DFG Funding details: Agence Nationale de la Recherche, ANR, ANR-10-INBS-04, PRC-2018 REPAIRCHROM Funding details: Magyar Tudományos Akadémia, MTA, LP2017-11/2017 Funding details: Fondation ARC pour la Recherche sur le Cancer, ARC Funding details: Max-Planck-Gesellschaft, MPG, AbD33205, AbD33641, AbD33644, AbD34251, AbD43647 Funding details: Institut Universitaire de France, IUF Funding details: Institut National Du Cancer, INCa, PLBIO-2019 Funding details: Horizon 2020, 864117 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, K128239, K143248 Funding text 1: We thank Ilian Atanassov and Xinping Li (MPI-AGE Proteomics Facility), the MPI-AGE FACS/Imaging Facility, and Steffen Lawo (MPI-AGE CRISPR Facility) for help with proteomic analyses, immunofluorescence experiments, and the validation of RNF114-KO cells, respectively. We thank Domagoj Baretic and Evgeniia Prokhorova for providing recombinant RNF114, ALC1, and APLF. Matic laboratory was funded by the European Research Council ( ERC ) under the European Union's Horizon 2020 research and innovation programme (consolidator grant nbPTMs, agreement No. 864117 to I.M.), DFG (CECAD; grant EXC229 to I.M.), Marie Sklodowska-Curie program (grant 657501 to J.J.B.), and EMBO-YIP (to I.M.). We thank the Microscopy-Rennes-Imaging Center (BIOSIT, Université Rennes 1), members of France-BioImaging supported by the French National Research Agency (ANR-10-INBS-04), for providing access to imaging, and S. Dutertre and X. Pinson for technical assistance. S.H.’s group received financial support from the Agence Nationale de la Recherche ( PRC-2018 REPAIRCHROM), the Institut National du Cancer ( PLBIO-2019 ), and the Institut Universitaire de France . R.S. is supported by the Fondation ARC ( PDF20181208405 ). Timinszky laboratory is supported by the Hungarian Academy of Sciences ( LP2017-11/2017 ) and the National Research Development and Innovation Office ( K128239 and K143248 ). O’Sullivan laboratory is funded by NCI ( R01CA262316 and R01CA207209 ). I.A. is funded by the Wellcome Trust (grants 101794 and 210634 ), the Ovarian Cancer Research Alliance ( 813369 ), BBSRC ( BB/R007195/1 ), and CRUK ( C35050/A22284 ). Funding text 2: We thank Ilian Atanassov and Xinping Li (MPI-AGE Proteomics Facility), the MPI-AGE FACS/Imaging Facility, and Steffen Lawo (MPI-AGE CRISPR Facility) for help with proteomic analyses, immunofluorescence experiments, and the validation of RNF114-KO cells, respectively. We thank Domagoj Baretic and Evgeniia Prokhorova for providing recombinant RNF114, ALC1, and APLF. Matic laboratory was funded by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (consolidator grant nbPTMs, agreement No. 864117 to I.M.), DFG (CECAD; grant EXC229 to I.M.), Marie Sklodowska-Curie program (grant 657501 to J.J.B.), and EMBO-YIP (to I.M.). We thank the Microscopy-Rennes-Imaging Center (BIOSIT, Université Rennes 1), members of France-BioImaging supported by the French National Research Agency (ANR-10-INBS-04), for providing access to imaging, and S. Dutertre and X. Pinson for technical assistance. S.H.’s group received financial support from the Agence Nationale de la Recherche (PRC-2018 REPAIRCHROM), the Institut National du Cancer (PLBIO-2019), and the Institut Universitaire de France. R.S. is supported by the Fondation ARC (PDF20181208405). Timinszky laboratory is supported by the Hungarian Academy of Sciences (LP2017-11/2017) and the National Research Development and Innovation Office (K128239 and K143248). O'Sullivan laboratory is funded by NCI (R01CA262316 and R01CA207209). I.A. is funded by the Wellcome Trust (grants 101794 and 210634), the Ovarian Cancer Research Alliance (813369), BBSRC (BB/R007195/1), and CRUK (C35050/A22284). I.M. conceived the project. I.M. S.H. and E.J.L. designed research. H.D. E.J.L. and J.J.B. designed the phage-display strategy, and selected and validated the antibodies and the SpyTag formats. E.J.L. J.J.B. and T.C. performed proteomics analyses. H.D. established the bead-loading/Fab system. E.J.L. H.D. C.L. R.S. E.P.J. C.M. and A.R.W. performed immunofluorescence and live-cell imaging experiments. A.K. generated the RNF114 KO cell line. A.R.W. M.L.L. and R.J.O. performed telomere-related experiments. R.F.-B. and G.T. performed the NHEJ reporter assay. M.S. and I.A. provided recombinant proteins and performed the experiments with ADP-ribosylated gDNA. E.J.L. C.L. A.P. C.M. and H.D. performed immunoprecipitation and immunoblotting experiments. S.H. performed the FCS experiments. I.M. and E.J.L. prepared the manuscript with input from all authors. E.J.L. H.D. J.J.B. T.C. and I.M. declare the following competing financial interests: Max-Planck-Innovation, the technology transfer center of the Max Planck Society, has licensed the antibodies AbD33204, AbD33205, AbD33644, AbD34251, AbD33641, and AbD43647 to Bio-Rad Laboratories. We support inclusive, diverse, and equitable conduct of research. One or more of the authors of this paper self-identifies as a member of the LGBTQIA+ community. AB - PARP1, an established anti-cancer target that regulates many cellular pathways, including DNA repair signaling, has been intensely studied for decades as a poly(ADP-ribosyl)transferase. Although recent studies have revealed the prevalence of mono-ADP-ribosylation upon DNA damage, it was unknown whether this signal plays an active role in the cell or is just a byproduct of poly-ADP-ribosylation. By engineering SpyTag-based modular antibodies for sensitive and flexible detection of mono-ADP-ribosylation, including fluorescence-based sensors for live-cell imaging, we demonstrate that serine mono-ADP-ribosylation constitutes a second wave of PARP1 signaling shaped by the cellular HPF1/PARP1 ratio. Multilevel chromatin proteomics reveals histone mono-ADP-ribosylation readers, including RNF114, a ubiquitin ligase recruited to DNA lesions through a zinc-finger domain, modulating the DNA damage response and telomere maintenance. Our work provides a technological framework for illuminating ADP-ribosylation in a wide range of applications and biological contexts and establishes mono-ADP-ribosylation by HPF1/PARP1 as an important information carrier for cell signaling. © 2023 The Author(s) LA - English DB - MTMT ER - TY - JOUR AU - Fajka-Boja, Roberta AU - Szebeni, Gábor AU - Hunyadi-Gulyás Éva, Csilla AU - Puskás, László AU - Katona, Róbert László TI - Polyploid Adipose Stem Cells Shift the Balance of IGF1/IGFBP2 to Promote the Growth of Breast Cancer JF - FRONTIERS IN ONCOLOGY J2 - FRONT ONCOL VL - 10 PY - 2020 PG - 8 SN - 2234-943X DO - 10.3389/fonc.2020.00157 UR - https://m2.mtmt.hu/api/publication/31183285 ID - 31183285 N1 - Cited By :2 Export Date: 10 February 2021 Correspondence Address: Katona, R.L.; Artificial Chromosome and Stem Cell Research Laboratory, Hungary; email: katona.robert@brc.hu LA - English DB - MTMT ER - TY - JOUR AU - Li, Yang AU - James, Sharmy J AU - Wyllie, David H AU - Wynne, Claire AU - Czibula, Ágnes AU - Bukhari, Ahmed AU - Pye, Katherine AU - Bte Mustafah, Seri Musfirah AU - Fajka-Boja, Roberta AU - Szabó, Enikő AU - Angyal, Adrienn AU - Hegedűs, Zoltán AU - Kovács, László AU - Hill, Adrian V S AU - Jefferies, Caroline A AU - Wilson, Heather L AU - Yongliang, Zhang AU - Kiss-Tóth, Endre TI - TMEM203 is a binding partner and regulator of STING-mediated inflammatory signaling in macrophages JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA J2 - P NATL ACAD SCI USA VL - 116 PY - 2019 IS - 33 SP - 16479 EP - 16488 PG - 10 SN - 0027-8424 DO - 10.1073/pnas.1901090116 UR - https://m2.mtmt.hu/api/publication/30750520 ID - 30750520 AB - Regulation of IFN signaling is critical in host recognition and response to pathogens while its dysregulation underlies the pathogenesis of several chronic diseases. STimulator of IFN Genes (STING) has been identified as a critical mediator of IFN inducing innate immune pathways, but little is known about direct coregulators of this protein. We report here that TMEM203, a conserved putative transmembrane protein, is an intracellular regulator of STING-mediated signaling. We show that TMEM203 interacts, functionally cooperates, and comigrates with STING following cell stimulation, which in turn leads to the activation of the kinase TBK1, and the IRF3 transcription factor. This induces target genes in macrophages, including IFN-β. Using Tmem203 knockout bone marrow-derived macrophages and transient knockdown of TMEM203 in human monocyte-derived macrophages, we show that TMEM203 protein is required for cGAMP-induced STING activation. Unlike STING, TMEM203 mRNA levels are elevated in T cells from patients with systemic lupus erythematosus, a disease characterized by the overexpression of type I interferons. Moreover, TMEM203 mRNA levels are associated with disease activity, as assessed by serum levels of the complement protein C3. Identification of TMEM203 sheds light into the control of STING-mediated innate immune responses, providing a potential novel mechanism for therapeutic interventions in STING-associated inflammatory diseases. LA - English DB - MTMT ER - TY - JOUR AU - Fajka-Boja, Roberta AU - Marton, Annamária AU - Tóth, Anna AU - Blazsó, Péter AU - Tubak, Vilmos AU - Bálint, Balázs AU - Nagy, István AU - Hegedűs, Zoltán AU - Vizler, Csaba AU - Katona, Róbert László TI - Adipose stem cells may promote cancer progression JF - RESEARCH OUTREACH J2 - RO VL - 2019 PY - 2019 SP - 6 EP - 9 PG - 4 SN - 2517-701X DO - 10.32907/RO-106-110113 UR - https://m2.mtmt.hu/api/publication/30693937 ID - 30693937 LA - English DB - MTMT ER - TY - JOUR AU - Fajka-Boja, Roberta AU - Marton, Annamária AU - Tóth, Anna AU - Blazsó, Péter AU - Tubak, Vilmos AU - Bálint, Balázs AU - Nagy, István AU - Hegedűs, Zoltán AU - Vizler, Csaba AU - Katona, Róbert László TI - Increased insulin-like growth factor 1 production by polyploid adipose stem cells promotes growth of breast cancer cells JF - BMC CANCER J2 - BMC CANCER VL - 18 PY - 2018 PG - 12 SN - 1471-2407 DO - 10.1186/s12885-018-4781-z UR - https://m2.mtmt.hu/api/publication/3411662 ID - 3411662 LA - English DB - MTMT ER - TY - JOUR AU - Szebeni, Gábor AU - Balázs, Á AU - Madarász, I AU - Pócz, G AU - Ayaydin, Ferhan AU - Kanizsai, Iván AU - Fajka-Boja, Roberta AU - Alföldi, Róbert AU - Hackler, László AU - Puskás, László TI - Achiral Mannich-base curcumin analogs induce unfolded protein response and mitochondrial membrane depolarization in PANC-1 cells JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 18 PY - 2017 IS - 10 PG - 16 SN - 1661-6596 DO - 10.3390/ijms18102105 UR - https://m2.mtmt.hu/api/publication/3284909 ID - 3284909 N1 - Megjegyzés-27115019 N1 Funding details: BO/00139/17/8, MTA, Magyar Tudományos AkadémiaUR - https://www.scopus.com/inward/record.uri?eid=2-s2.0-85031101118&doi=10.3390%2fijms18102105&partnerID=40&md5=91398dce9d4e3934200512d7029302d1 WoS:hiba:000414671800089 2019-03-03 20:57 cikkazonosító nem egyezik Avidin Ltd., Alsó kikötő sor 11/D, Szeged, H-6726, Hungary Laboratory of Functional Genomics, Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary Cellular Imaging Laboratory, Institute of Plant Biology, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary Artificial Chromosome and Stem Cell Research Laboratory, Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary Cited By :16 Export Date: 21 January 2021 Correspondence Address: Puskás, L.G.; Avidin Ltd., Alsó kikötő sor 11/D, Hungary; email: laszlo@avidinbiotech.com Avidin Ltd., Alsó kikötő sor 11/D, Szeged, H-6726, Hungary Laboratory of Functional Genomics, Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary Cellular Imaging Laboratory, Institute of Plant Biology, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary Artificial Chromosome and Stem Cell Research Laboratory, Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary Cited By :16 Export Date: 10 February 2021 Correspondence Address: Puskás, L.G.; Avidin Ltd., Alsó kikötő sor 11/D, Hungary; email: laszlo@avidinbiotech.com LA - English DB - MTMT ER - TY - JOUR AU - Hetényi, Anasztázia AU - Hegedüs, Zsófia AU - Fajka-Boja, Roberta AU - Monostori, Éva AU - E Kövér, Katalin AU - Martinek, Tamás TI - Target-specific NMR detection of protein–ligand interactions with antibody-relayed 15N-group selective STD JF - JOURNAL OF BIOMOLECULAR NMR J2 - J BIOMOL NMR VL - 66 PY - 2016 IS - 4 SP - 227 EP - 232 PG - 6 SN - 0925-2738 DO - 10.1007/s10858-016-0076-3 UR - https://m2.mtmt.hu/api/publication/3148106 ID - 3148106 N1 - Funding Agency and Grant Number: Hungarian Research Foundation OTKA [PD83600, K105459]; Hungarian Academy of Sciences, Lendulet program [LP-2011-009]; European Union; State of Hungary; European Social Fund [TAMOP-4.2.4.A/2-11/1-2012-0001]; EU; European Regional Development Fund [GINOP-2.3.3-15-2016-00004, GINOP-2.3.3-15-2016-00010]\n Funding text: This work was supported by the Hungarian Research Foundation OTKA projects PD83600 and K105459 and the Hungarian Academy of Sciences, Lendulet program (LP-2011-009). This research was supported by the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TAMOP-4.2.4.A/2-11/1-2012-0001 'National Excellence Program'. The research was supported by the EU and co-financed by the European Regional Development Fund under the projects GINOP-2.3.3-15-2016-00004 and GINOP-2.3.3-15-2016-00010.\n Funding Agency and Grant Number: Hungarian Research Foundation OTKA [PD83600, K105459]; Hungarian Academy of Sciences, Lendulet program [LP-2011-009]; European Union; State of Hungary; European Social Fund [TAMOP-4.2.4.A/2-11/1-2012-0001]; EU; European Regional Development Fund [GINOP-2.3.3-15-2016-00004, GINOP-2.3.3-15-2016-00010] Funding text: This work was supported by the Hungarian Research Foundation OTKA projects PD83600 and K105459 and the Hungarian Academy of Sciences, Lendulet program (LP-2011-009). This research was supported by the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TAMOP-4.2.4.A/2-11/1-2012-0001 'National Excellence Program'. The research was supported by the EU and co-financed by the European Regional Development Fund under the projects GINOP-2.3.3-15-2016-00004 and GINOP-2.3.3-15-2016-00010. AB - Fragment-based drug design has been successfully applied to challenging targets where the detection of the weak protein-ligand interactions is a key element. H-1 saturation transfer difference (STD) NMR spectroscopy is a powerful technique for this work but it requires pure homogeneous proteins as targets. Monoclonal antibody (mAb)-relayed N-15-GS STD spectroscopy has been developed to resolve the problem of protein mixtures and impure proteins. A N-15-labelled target-specific mAb is selectively irradiated and the saturation is relayed through the target to the ligand. Tests on the anti-Gal-1 mAb/Gal-1/lactose system showed that the approach is experimentally feasible in a reasonable time frame. This method allows detection and identification of binding molecules directly from a protein mixture in a multicomponent system. LA - English DB - MTMT ER - TY - JOUR AU - Fajka-Boja, Roberta AU - Suhajdáné Urbán, Veronika AU - Szebeni, Gábor AU - Czibula, Ágnes AU - Blaskó, Andrea AU - Kriston-Pál, Éva AU - Makra, Ildikó AU - Hornung, Ákos AU - Szabó, Enikő AU - Uher, Ferenc AU - Than, Nándor Gábor AU - Monostori, Éva TI - Galectin-1 is a local but not systemic immunomodulatory factor in mesenchymal stromal cells JF - CYTOTHERAPY J2 - CYTOTHERAPY VL - 18 PY - 2016 IS - 3 SP - 360 EP - 370 PG - 11 SN - 1465-3249 DO - 10.1016/j.jcyt.2015.12.004 UR - https://m2.mtmt.hu/api/publication/3024122 ID - 3024122 AB - BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have powerful immunosuppressive activity. This function of MSCs is attributed to plethora of the expressed immunosuppressive factors, such as galectin-1 (Gal-1), a pleiotropic lectin with robust anti-inflammatory effect. Nevertheless, whether Gal-1 renders or contributes to the immunosuppressive effect of MSCs has not been clearly established. Therefore, this question was the focus of a complex study. METHODS: MSCs were isolated from bone marrows of wild-type and Gal-1 knockout mice and their in vitro anti-proliferative and apoptosis-inducing effects on activated T cells were examined. The in vivo immunosuppressive activity was tested in murine models of type I diabetes and delayed-type hypersensitivity. RESULTS: Both Gal-1-expressing and -deficient MSCs inhibited T-cell proliferation. Inhibition of T-cell proliferation by MSCs was mediated by nitric oxide but not PD-L1 or Gal-1. In contrast, MSC-derived Gal-1 triggered apoptosis in activated T cells that were directly coupled to MSCs, representing a low proportion of the T-cell population. Furthermore, absence of Gal-1 in MSCs did not affect their in vivo immunosuppressive effect. CONCLUSIONS: These results serve as evidence that Gal-1 does not play a role in the systemic immunosuppressive effect of MSCs. However, a local contribution of Gal-1 to modulation of T-cell response by direct cell-to-cell interaction cannot be excluded. Notably, this study serves a good model to understand how the specificity of a pleiotropic protein depends on the type and localization of the producing effector cell and its target. LA - English DB - MTMT ER - TY - JOUR AU - Fajka-Boja, Roberta AU - Czibula, Ágnes AU - Monostori, Éva TI - Genetics, molecular and cell biology of apoptotic cell death JF - ACTA BIOLOGICA SZEGEDIENSIS J2 - ACTA BIOL SZEGED VL - 59 PY - 2015 IS - Suppl. 1. SP - 143 EP - 156 PG - 14 SN - 1588-385X UR - https://m2.mtmt.hu/api/publication/2948585 ID - 2948585 LA - English DB - MTMT ER -