TY - JOUR AU - Mérey, Mihály AU - Fajka-Boja, Roberta AU - Imre, Gergely AU - Gudmann, Péter AU - Török, Zsolt AU - Mátés, Lajos AU - Czibula, Ágnes AU - Timinszky, Gyula TI - TARG1 affects EGFR signaling through the regulation of RNA metabolism JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 15 PY - 2025 IS - 1 PG - 14 SN - 2045-2322 DO - 10.1038/s41598-025-08010-5 UR - https://m2.mtmt.hu/api/publication/36226732 ID - 36226732 N1 - Funding Agency and Grant Number: HUN-REN Biological Research Centre, Szeged; National Research Development and Innovation Office [K128239, K143248, TKP2021-EGA09] Funding text: Open access funding provided by HUN-REN Biological Research Centre, Szeged. Open access funding provided by HUN-REN Biological Research Centre, Szeged. The work in the Timinszky laboratory was supported by the National Research Development and Innovation Office (K128239 and K143248). P.G and Z.T. acknowledge support from the National Research Development and Innovation Office (TKP2021-EGA09). AB - Epidermal Growth Factor Receptor (EGFR) signaling plays a central role in cell proliferation, migration, and survival. Emerging evidence suggests a connection between ADP-ribosylation and EGFR regulation. Previous studies implicated PARP’s role in EGFR signaling, but the participation of ADP(ribosyl)hydrolases in it, that can revert their enzymatic modifications, still remained elusive. The role of TARG1, a macrodomain-containing hydrolase, that has been implicated in RNA metabolism, and cellular stress response, but was not studied in EGFR signaling before. Here, we investigate the impact of TARG1 depletion in U2-OS osteosarcoma cells using knockout (KO) and knockdown (KD) models. We find that TARG1 loss reduces both EGFR protein and mRNA levels. Our results show increased mRNA turnover and altered RNA distribution and translation in TARG1 KO cells, suggesting that TARG1 influences RNA metabolism and translational regulation. Notably, TARG1-deficient cells exhibit heightened sensitivity to MEK1/2 inhibition, indicating potential crosstalk between TARG1 and the Ras/MEK/ERK pathway. These findings suggest that TARG1, and possibly ADP-ribosylation, regulate EGFR expression and translation through RNA biogenesis-mediated mechanisms, highlighting its potential role in cancer cell signaling and survival. LA - English DB - MTMT ER - TY - JOUR AU - Imre, Gergely AU - Takács, Bertalan Vilmos AU - Czipa, Erik AU - Drubi, Andrea AU - Jaksa, Gábor AU - Latinovics, Dóra AU - Nagy, Andrea AU - Karkas, Réka AU - Hudoba, Liza AU - Vásárhelyi, Bálint Márk AU - Pankotai-Bodó, Gabriella AU - Blastyák, András AU - Hegedűs, Zoltán AU - Germán, Péter AU - Bálint, Balázs AU - Abdullah, Khaldoon Sadiq Ahmed AU - Kopasz, Anna Georgina AU - Kovács, Anita Kármen AU - Nagy, László AU - Sükösd, Farkas AU - Pintér, Lajos AU - Rülicke, Thomas AU - Barta, Endre AU - Nagy, István AU - Haracska, Lajos AU - Mátés, Lajos TI - Prolonged activity of the transposase helper may raise safety concerns during DNA transposon-based gene therapy JF - MOLECULAR THERAPY-METHODS AND CLINICAL DEVELOPMENT J2 - MOL THER-METH CLIN D VL - 29 PY - 2023 SP - 145 EP - 159 PG - 15 SN - 2329-0501 DO - 10.1016/j.omtm.2023.03.003 UR - https://m2.mtmt.hu/api/publication/33708483 ID - 33708483 AB - DNA transposon-based gene delivery vectors represent a promising new branch of randomly integrating vector development for gene therapy. For the side-by-side evaluation of the piggyBac and Sleeping Beauty systems—the only DNA transposons currently employed in clinical trials—during therapeutic intervention, we treated the mouse model of tyrosinemia type I with liver-targeted gene delivery using both transposon vectors. For genome-wide mapping of transposon insertion sites we developed a new next-generation sequencing procedure called streptavidin-based enrichment sequencing, which allowed us to identify approximately one million integration sites for both systems. We revealed that a high proportion of piggyBac integrations are clustered in hot regions and found that they are frequently recurring at the same genomic positions among treated animals, indicating that the genome-wide distribution of Sleeping Beauty-generated integrations is closer to random. We also revealed that the piggyBac transposase protein exhibits prolonged activity, which predicts the risk of oncogenesis by generating chromosomal double-strand breaks. Safety concerns associated with prolonged transpositional activity draw attention to the importance of squeezing the active state of the transposase enzymes into a narrower time window. LA - English DB - MTMT ER - TY - JOUR AU - Kopasz, Anna Georgina AU - Pusztai, Dávid AU - Karkas, Réka AU - Hudoba, Liza AU - Abdullah, Khaldoon Sadiq Ahmed AU - Imre, Gergely AU - Pankotai-Bodó, Gabriella AU - Migh, Ede AU - Nagy, Andrea AU - Kriston, András AU - Germán, Péter AU - Drubi, Andrea AU - Molnár, Anna AU - Fekete, Ildikó AU - Dani, Virág Éva AU - Ocsovszki, Imre AU - Puskás, László AU - Horváth, Péter AU - Sükösd, Farkas AU - Mátés, Lajos TI - A versatile transposon-based technology to generate loss- and gain-of-function phenotypes in the mouse liver JF - BMC BIOLOGY J2 - BMC BIOL VL - 20 PY - 2022 IS - 1 PG - 17 SN - 1741-7007 DO - 10.1186/s12915-022-01262-x UR - https://m2.mtmt.hu/api/publication/32773206 ID - 32773206 N1 - Funding Agency and Grant Number: Momentum Programme of the Hungarian Academy of Sciences [LP2015-5/2015]; National Research, Development and Innovation Office (Hungary)National Research, Development & Innovation Office (NRDIO) - Hungary [GINOP-2.3.2-15-2016-00024]; LENDULET-BIOMAG [2018342]; European Regional Development FundEuropean Commission [GINOP-2.3.2-15-201600026]; COMPASS-ERA PerMed H2020; CZI Deep Visual Proteomics; H2020-DiscovAir; ELKH-Excellence grant; New National Excellence Program of the Ministry for Innovation and Technology from the National Research, Development and Innovation Fund [UNKP-20-3-SZTE-84]; Szeged Scientists Academy under Hungarian Ministry of Innovation and Technology [FEIF/646-4/2021-ITM_SZERZ]; New National Excellence Program of the Ministry for Innovation and Technology of Hungary [UNKP-20-2 -SZTE-438] Funding text: This work was supported by the Momentum Programme of the Hungarian Academy of Sciences [LP2015-5/2015] and by the National Research, Development and Innovation Office (Hungary) grant [GINOP-2.3.2-15-2016-00024]. PH, EM, and AK acknowledge support from the LENDULET-BIOMAG Grant [2018342], from the European Regional Development Fund (GINOP-2.3.2-15-201600026), from COMPASS-ERA PerMed H2020, from CZI Deep Visual Proteomics, from H2020-DiscovAir, and from ELKH-Excellence grant. RK was supported by the UNKP-20-3-SZTE-84 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. AGK was supported by the Szeged Scientists Academy under the sponsorship of the Hungarian Ministry of Innovation and Technology (FEIF/646-4/2021-ITM_SZERZ) and the New National Excellence Program of the Ministry for Innovation and Technology of Hungary (UNKP-20-2 -SZTE-438). AB - Understanding the contribution of gene function in distinct organ systems to the pathogenesis of human diseases in biomedical research requires modifying gene expression through the generation of gain- and loss-of-function phenotypes in model organisms, for instance, the mouse. However, methods to modify both germline and somatic genomes have important limitations that prevent easy, strong, and stable expression of transgenes. For instance, while the liver is remarkably easy to target, nucleic acids introduced to modify the genome of hepatocytes are rapidly lost, or the transgene expression they mediate becomes inhibited due to the action of effector pathways for the elimination of exogenous DNA. Novel methods are required to overcome these challenges, and here we develop a somatic gene delivery technology enabling long-lasting high-level transgene expression in the entire hepatocyte population of mice. LA - English DB - MTMT ER - TY - GEN AU - Karkas, R AU - Blastyák, A AU - Hudoba, L AU - Bakné, Drubi A AU - Imre, Gergely AU - Mátés, L TI - Comparison of the DNA transposon-based approaches in the gene therapy of the Mouse Model of Tyrosinemia Type I PY - 2021 UR - https://m2.mtmt.hu/api/publication/32528660 ID - 32528660 LA - English DB - MTMT ER - TY - GEN AU - Imre, Gergely AU - Hudoba, L AU - Nagy, A AU - Balazs, B AU - Nagy, I AU - Rülicke, T AU - Mates, L TI - Somatic-transgenic mouse model to introduce random genome-wide deletions PY - 2016 UR - https://m2.mtmt.hu/api/publication/31614585 ID - 31614585 LA - English DB - MTMT ER - TY - JOUR AU - Nagy, Andrea AU - Imre, Gergely AU - Mátés, Lajos TI - Transposon-based gene delivery vectors for gene therapy JF - ACTA BIOLOGICA SZEGEDIENSIS J2 - ACTA BIOL SZEGED VL - 59 PY - 2015 IS - Suppl 2 SP - 247 EP - 260 PG - 14 SN - 1588-385X UR - https://m2.mtmt.hu/api/publication/2998018 ID - 2998018 AB - The first gene therapy clinical trials were initiated more than two decades ago thanks to the previous development of viral vectors that allow high efficiency gene transfer into mammalian cells. Since then the application of viral gene transfer has been a successful treatment option for a variety of diseases. Hematopoietic stem cells (HSCs) represent the most frequently targeted cell population for the treatment of severe monogenic diseases as their gene therapeutic correction is a valid alternative to conventional HSC transplantation when a compatible donor is not available. Indeed, viral gene transfer was successfully applied in HSC-based ex vivo gene therapy of the blood and immune systems, albeit several studies have exposed serious adverse effects that were caused by the therapeutic vector induced inappropriate activation of proto-oncogenes. After these failures, researchers have developed new types of randomly integrating vectors that have proven safer in preclinical studies, which is consistent with interim reports of clinical trials also foreshadowing that they potentially have an improved safety profile. This review focuses on new and clinically relevant DNA transposon-based gene delivery vectors, and compares their properties with those of the old and new generation viral vectors. LA - English DB - MTMT ER - TY - GEN AU - Nagy, A AU - Hudoba, L AU - Imre, Gergely AU - Hegedus, K AU - Fekete, I AU - Rulicke, T AU - Mates, L TI - A novel transgenic organ model to screen for the genetic drivers of tumorgenesis PY - 2015 UR - https://m2.mtmt.hu/api/publication/31614602 ID - 31614602 LA - English DB - MTMT ER - TY - JOUR AU - Nagy, Gábor AU - Imre, Gergely AU - Csernetics, Árpád AU - Petkovits, Tamás AU - Nagy, László AU - Szekeres, András AU - Vágvölgyi, Csaba AU - Papp, Tamás TI - A prenyl pyrophosphate synthase gene from the zygomycete fungus, Gilbertella persicaria JF - ACTA BIOLOGICA SZEGEDIENSIS J2 - ACTA BIOL SZEGED VL - 55 PY - 2011 IS - 1 SP - 7 EP - 12 PG - 6 SN - 1588-385X UR - https://m2.mtmt.hu/api/publication/1939772 ID - 1939772 N1 - Megjegyzés-22370108 Chemicals/CAS: astaxanthin, 472-61-7; beta carotene, 7235-40-7; farnesyl trans transferase, 9032-58-0 Megjegyzés-23214237 N1 : Chemicals/CASastaxanthin, 472-61-7; beta carotene, 7235-40-7; farnesyl trans transferase, 9032-58-0 Department of Microbiology, University of Szeged, Szeged, Hungary FumoPrep Ltd., Mórahalom, Hungary Export Date: 17 July 2020 CODEN: ABSCC Correspondence Address: Papp, T.; Department of Microbiology, University of Szeged, Szeged, Hungary; email: pappt@bio.u-szeged.hu Chemicals/CAS: astaxanthin, 472-61-7; beta carotene, 7235-40-7; farnesyl trans transferase, 9032-58-0 LA - English DB - MTMT ER - TY - JOUR AU - Nagy, Gábor AU - Farkas, Anita AU - Imre, Gergely AU - Csernetics, Árpád AU - Vágvölgyi, Csaba AU - Papp, Tamás TI - HMG-CoA reductase genes of the carotenoid producing Mucor circinelloides JF - ACTA MICROBIOLOGICA ET IMMUNOLOGICA HUNGARICA J2 - ACTA MICROBIOL IMMUNOL HUNG VL - 58 PY - 2011 IS - Supplement 1 SP - 190 SN - 1217-8950 UR - https://m2.mtmt.hu/api/publication/1945835 ID - 1945835 LA - English DB - MTMT ER - TY - CHAP AU - Nagy, Gábor AU - Csernetics, Árpád AU - Imre, Gergely AU - Farkas, Anita AU - Vágvölgyi, Csaba AU - Papp, Tamás ED - Škrbić, B ED - Milanović, S TI - Characterization of HMG-CoA reductase genes of the carotenoid producing Mucor circinelloides T2 - 2nd CEFSER (Center of Excellence in Food Safety and Emerging Risks) Workshop Persistant Organic Pollutants in Food and the Environment [and] 26th Symposium on Recent Developments in Dairy Technology [and] BIOXEN seminar Novel Approaches for Environmental Protection PB - University of Novi Sad, Faculty of Technical Sciences CY - Novi Sad SN - 9788680995939 PY - 2011 SP - 54 UR - https://m2.mtmt.hu/api/publication/1945980 ID - 1945980 LA - English DB - MTMT ER -