TY - JOUR AU - Kovács, Ákos AU - Sükösd, Farkas AU - Kuthi, Levente AU - Boros, Imre Miklós AU - Vedelek, Balázs TI - Novel method for detecting frequent TERT promoter hot spot mutations in bladder cancer samples. JF - CLINICAL AND EXPERIMENTAL MEDICINE J2 - CLIN EXP MED VL - 24 PY - 2024 IS - 1 SP - 192 SN - 1591-8890 DO - 10.1007/s10238-024-01464-3 UR - https://m2.mtmt.hu/api/publication/35176626 ID - 35176626 AB - Telomerase reverse transcriptase promoter (TERTp) mutations are frequently targeted tumor markers, however, they reside in regions with high GC content, which poses challenges when examined with simple molecular techniques or even with next-generation sequencing (NGS). In bladder cancer (BC), TERTp mutations are particularly frequent, however, none of the available tools have demonstrated efficacy in detecting TERTp mutations via a simple noninvasive technique. Therefore, we developed a novel PCR-based method for the detection of the two most common TERTp mutations and demonstrated its use for the analysis of BC samples. The developed SHARD-PCR TERTp mutation detection technique requires PCR and restriction digestion steps that are easily implementable even in less well-equipped laboratories. Cell lines with known mutational status were utilized for method development. Matching urine and tumor tissue samples from BC patients were analyzed, and the results were validated by next-generation sequencing. Analysis of eighteen urine and corresponding tumor tissue samples by SHARD-PCR revealed perfect matches in sample pairs, which paralleled the corresponding NGS results: fourteen samples exhibited mutations at the -124 position, two samples showed mutations at the -146 position, and no mutations were detected in two samples. Our study serves as a proof-of-concept and is limited by its small sample size, nonetheless, it demonstrates that SHARD-PCR is a simple, economic and highly reliable method for detecting TERTp mutations, which are common in different cancer types. For bladder cancer, SHARD-PCR can be performed with the use of noninvasive samples and could replace or complement currently used techniques. LA - English DB - MTMT ER - TY - JOUR AU - Kovács, Zoltán AU - Bajusz, Csaba AU - Szabó, Anikó AU - Borkúti, Péter AU - Vedelek, Balázs AU - Benke, Reka AU - Lipinszki, Zoltán AU - Kristó, Ildikó AU - Vilmos, Péter TI - A bipartite NLS motif mediates the nuclear import of Drosophila moesin JF - FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY J2 - FRONT CELL DEV BIOL VL - 12 PY - 2024 PG - 14 SN - 2296-634X DO - 10.3389/fcell.2024.1206067 UR - https://m2.mtmt.hu/api/publication/34743202 ID - 34743202 N1 - Funding Agency and Grant Number: NKFIH (Hungarian National Research, Development and Innovation Office) through the National Laboratory for Biotechnology program [PD127968, LP2017-7/2017]; Hungarian Academy of Sciences Lendulet Grant; [2022-2.1.1-NL-2022-00008] Funding text: This work was supported by NKFIH (Hungarian National Research, Development and Innovation Office) through the National Laboratory for Biotechnology program, grant 2022-2.1.1-NL-2022-00008 (PV), and PD127968 (IK), and the Hungarian Academy of Sciences Lendulet Grant LP2017-7/2017 (ZL). AB - The ERM protein family, which consists of three closely related proteins in vertebrates, ezrin, radixin, and moesin (ERM), is an ancient and important group of cytoplasmic actin-binding and organizing proteins. With their FERM domain, ERMs bind various transmembrane proteins and anchor them to the actin cortex through their C-terminal F-actin binding domain, thus they are major regulators of actin dynamics in the cell. ERMs participate in many fundamental cellular processes, such as phagocytosis, microvilli formation, T-cell activation and tumor metastasis. We have previously shown that, besides its cytoplasmic activities, the single ERM protein of Drosophila melanogaster, moesin, is also present in the cell nucleus, where it participates in gene expression and mRNA export. Here we study the mechanism by which moesin enters the nucleus. We show that the nuclear import of moesin is an NLS-mediated, active process. The nuclear localization sequence of the moesin protein is an evolutionarily highly conserved, conventional bipartite motif located on the surface of the FERM domain. Our experiments also reveal that the nuclear import of moesin does not require PIP2 binding or protein activation, and occurs in monomeric form. We propose, that the balance between the phosphorylated and non-phosphorylated protein pools determines the degree of nuclear import of moesin. LA - English DB - MTMT ER - TY - JOUR AU - Datki, Zsolt László AU - Darula, Zsuzsanna AU - Vedelek, Viktor AU - Hunyadi-Gulyás Éva, Csilla AU - Dingmann, Brian J. AU - Vedelek, Balázs AU - Kalman, Janos AU - Urbán, Péter AU - Gyenesei, Attila AU - Galik-Olah, Zita AU - Gálik, Bence AU - Sinka, Rita TI - Biofilm formation initiating rotifer-specific biopolymer and its predicted components JF - INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES J2 - INT J BIOL MACROMOL VL - 253 PY - 2023 IS - Part 5 PG - 14 SN - 0141-8130 DO - 10.1016/j.ijbiomac.2023.127157 UR - https://m2.mtmt.hu/api/publication/34334193 ID - 34334193 N1 - Megosztott szerzőség AB - The rotifer-specific biopolymer, namely Rotimer, is a recently discovered group of the biomolecule family. Rotimer has an active role in the biofilm formation initiated by rotifers (e.g., Euchlanis dilatata or Adineta vaga) or in the female-male sexual interaction of monogononts. To understand the Ca2+- and polarity-dependent formation of this multifunctional viscoelastic material, it is essential to explore its molecular composition. The investigation of the rotifer-enhanced biofilm and Rotimer-inductor conglomerate (RIC) formation yielded several protein candidates to predict the Rotimer-specific main components. The exudate of E. dilatata males was primarily applied from different biopolimer-containing samples (biofilm or RIC). The advantage of males over females lies in their degenerated digestive system and simple anatomy. Thus, their exudate is less contaminated with food and endosymbiont elements. The sequenced and annotated genome and transcriptome of this species opened the way for identifying Rotimer proteins by mass spectrometry. The predicted rotifer-biopolymer forming components are SCO-spondins and 14-3-3 protein. The characteristics of Rotimer are similar to Reissner's fiber, which is found in the central nervous system of vertebrates and is mainly formed from SCO-spondins. This molecular information serves as a starting point for its interdisciplinary investigation and application in biotechnology, biomedicine, or neurodegeneration-related drug development. LA - English DB - MTMT ER - TY - JOUR AU - Vedelek, Viktor AU - Vedelek, Balázs AU - Lőrincz, Péter AU - Juhász, Gábor AU - Sinka, Rita TI - A comparative analysis of fruit fly and human glutamate dehydrogenases in Drosophila melanogaster sperm development JF - FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY J2 - FRONT CELL DEV BIOL VL - 11 PY - 2023 PG - 16 SN - 2296-634X DO - 10.3389/fcell.2023.1281487 UR - https://m2.mtmt.hu/api/publication/34239207 ID - 34239207 N1 - Funding Agency and Grant Number: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by NKFIH (PD137914 to VV, K132155 to RS, and FK138851 to PL), National Research, Development, and Innovation Offi [PD137914, K132155, FK138851]; NKFIH [2022-2.1.1-NL-2022-00008, EKA 2022/045-P101-2, LP 2022-13/2022]; National Research, Development, and Innovation Office of Hungary (Biotechnology National Laboratory) Funding text: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by NKFIH (PD137914 to VV, K132155 to RS, and FK138851 to PL), National Research, Development, and Innovation Office of Hungary (Biotechnology National Laboratory 2022-2.1.1-NL-2022-00008 to GJ), and Eotvos Lorand University Excellence Fund (EKA 2022/045-P101-2), MTA-t (LP 2022-13/2022) to PL.r The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by NKFIH (PD137914 to VV, K132155 to RS, and FK138851 to PL), National Research, Development, and Innovation Office of Hungary (Biotechnology National Laboratory 2022-2.1.1-NL-2022-00008 to GJ), and Eotvos Lorand University Excellence Fund (EKA 2022/045-P101-2), MTA-t (LP 2022-13/2022) to PL. AB - Glutamate dehydrogenases are enzymes that take part in both amino acid and energy metabolism. Their role is clear in many biological processes, from neuronal function to cancer development. The putative testis-specific Drosophila glutamate dehydrogenase, Bb8, is required for male fertility and the development of mitochondrial derivatives in spermatids. Testis-specific genes are less conserved and could gain new functions, thus raising a question whether Bb8 has retained its original enzymatic activity. We show that while Bb8 displays glutamate dehydrogenase activity, there are significant functional differences between the housekeeping Gdh and the testis-specific Bb8. Both human GLUD1 and GLUD2 can rescue the bb8 ms mutant phenotype, with superior performance by GLUD2. We also tested the role of three conserved amino acids observed in both Bb8 and GLUD2 in Gdh mutants, which showed their importance in the glutamate dehydrogenase function. The findings of our study indicate that Drosophila Bb8 and human GLUD2 could be novel examples of convergent molecular evolution. Furthermore, we investigated the importance of glutamate levels in mitochondrial homeostasis during spermatogenesis by ectopic expression of the mitochondrial glutamate transporter Aralar1, which caused mitochondrial abnormalities in fly spermatids. The data presented in our study offer evidence supporting the significant involvement of glutamate metabolism in sperm development. LA - English DB - MTMT ER - TY - JOUR AU - Vedelek, Balázs AU - Kovács, Ákos AU - Boros, Imre Miklós TI - Evolutionary mode for the functional preservation of fast-evolving Drosophila telomere capping proteins JF - OPEN BIOLOGY J2 - OPEN BIOL VL - 11 PY - 2021 IS - 11 PG - 11 SN - 2046-2441 DO - 10.1098/rsob.210261 UR - https://m2.mtmt.hu/api/publication/32517518 ID - 32517518 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office-NKFIHNational Research, Development & Innovation Office (NRDIO) - Hungary [GINOP-2.3.2-152016-00020, GINOP-2.3.2-15-2016-00032, OTKA K116372]; Szeged Scientists Academy; Hungarian Ministry of Innovation and Technology [FEIF/646-4/2021-ITM_SZERZ] Funding text: The financial support of the National Research, Development and Innovation Office-NKFIH through grant nos. GINOP-2.3.2-152016-00020, GINOP-2.3.2-15-2016-00032 and OTKA K116372 to I.M.B. and B.V. are greatly appreciated. This research work was conducted with the support of the Szeged Scientists Academy under the sponsorship of the Hungarian Ministry of Innovation and Technology (grant no. FEIF/646-4/2021-ITM_SZERZ). AB - DNA end protection is fundamental for the long-term preservation of the genome. In vertebrates the Shelterin protein complex protects telomeric DNA ends, thereby contributing to the maintenance of genome integrity. In the Drosophila genus, this function is thought to be performed by the Terminin complex, an assembly of fast-evolving subunits. Considering that DNA end protection is fundamental for successful genome replication, the accelerated evolution of Terminin subunits is counterintuitive, as conservation is supposed to maintain the assembly and concerted function of the interacting partners. This problem extends over Drosophila telomere biology and provides insight into the evolution of protein assemblies. In order to learn more about the mechanistic details of this phenomenon we have investigated the intra- and interspecies assemblies of Verrocchio and Modigliani, two Terminin subunits using in vitro assays. Based on our results and on homology-based three-dimensional models for Ver and Moi, we conclude that both proteins contain Ob-fold and contribute to the ssDNA binding of the Terminin complex. We propose that the preservation of Ver function is achieved by conservation of specific amino acids responsible for folding or localized in interacting surfaces. We also provide here the first evidence on Moi DNA binding. LA - English DB - MTMT ER - TY - JOUR AU - Vedelek, Balázs AU - Maddali, Asha Kiran AU - Davenova, Nurgul AU - Vedelek, Viktor AU - Boros, Imre Miklós TI - TERT promoter alterations could provide a solution for Peto’s paradox in rodents JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 10 PY - 2020 IS - 1 PG - 13 SN - 2045-2322 DO - 10.1038/s41598-020-77648-0 UR - https://m2.mtmt.hu/api/publication/31677445 ID - 31677445 N1 - Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary Institute of Biochemistry, Biological Research Centre, Szeged, Hungary Institute of Genetics, Biological Research Centre, Szeged, Hungary Department of Genetics, University of Szeged, Szeged, Hungary Export Date: 13 January 2021 Correspondence Address: Boros, I.M.; Department of Biochemistry and Molecular Biology, University of SzegedHungary; email: borosi@bio.u-szeged.hu Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary Institute of Biochemistry, Biological Research Centre, Szeged, Hungary Institute of Genetics, Biological Research Centre, Szeged, Hungary Department of Genetics, University of Szeged, Szeged, Hungary Export Date: 15 February 2021 Correspondence Address: Boros, I.M.; Department of Biochemistry and Molecular Biology, Hungary; email: borosi@bio.u-szeged.hu Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary Institute of Biochemistry, Biological Research Centre, Szeged, Hungary Institute of Genetics, Biological Research Centre, Szeged, Hungary Department of Genetics, University of Szeged, Szeged, Hungary Export Date: 18 February 2021 Correspondence Address: Boros, I.M.; Department of Biochemistry and Molecular Biology, Hungary; email: borosi@bio.u-szeged.hu LA - English DB - MTMT ER - TY - JOUR AU - Henn, László AU - Szabó, Anikó AU - Imre, László AU - Román, Ádám AU - Ábrahám, Andrea AU - Vedelek, Balázs AU - Nánási, Péter Pál AU - Boros, Imre Miklós TI - Alternative linker histone permits fast paced nuclear divisions in early Drosophila embryo JF - NUCLEIC ACIDS RESEARCH J2 - NUCLEIC ACIDS RES VL - 48 PY - 2020 IS - 16 SP - 9007 EP - 9018 PG - 12 SN - 0305-1048 DO - 10.1093/nar/gkaa624 UR - https://m2.mtmt.hu/api/publication/31397830 ID - 31397830 AB - In most animals, the start of embryogenesis requires specific histones. In Drosophila linker histone variant BigH1 is present in early embryos. To uncover the specific role of this alternative linker histone at early embryogenesis, we established fly lines in which domains of BigH1 have been replaced partially or completely with that of H1. Analysis of the resulting Drosophila lines revealed that at normal temperature somatic H1 can substitute the alternative linker histone, but at low temperature the globular and C-terminal domains of BigH1 are essential for embryogenesis. In the presence of BigH1 nucleosome stability increases and core histone incorporation into nucleosomes is more rapid, while nucleosome spacing is unchanged. Chromatin formation in the presence of BigH1 permits the fast-paced nuclear divisions of the early embryo. We propose a model which explains how this specific linker histone ensures the rapid nucleosome reassembly required during quick replication cycles at the start of embryogenesis. LA - English DB - MTMT ER - TY - BOOK AU - Borsos, Barbara Nikolett AU - Vedelek, Balázs ED - Boros, Imre Miklós TI - Macromolecule design and manipulation - practical textbook PB - University of Szeged CY - Szeged PY - 2018 SP - 304 UR - https://m2.mtmt.hu/api/publication/30969581 ID - 30969581 LA - English DB - MTMT ER - TY - CHAP AU - Vedelek, Balázs AU - Asha, Maddali Kiran AU - Boros, Imre Miklós ED - Dávis, Szüts ED - László, Buday ED - Róbert, Hohol ED - Gergely, Szakáts ED - Gabriella, Bánfalvi TI - A possible mechanism explaining the telomerase promoter inactivation in mammalian somatic cells T2 - FEBS3+: From molecules to living systems PB - Diamond Congress Kft. CY - Veszprém SN - 9786155270475 PY - 2018 SP - 68 EP - 68 PG - 1 UR - https://m2.mtmt.hu/api/publication/3415003 ID - 3415003 LA - English DB - MTMT ER - TY - THES AU - Vedelek, Balázs TI - A Drosophila telomer védelmét szolgáló fehérjék fajképzésben betöltött lehetséges szerepének vizsgálata PB - Szegedi Tudományegyetem (SZTE) PY - 2017 SP - 92 DO - 10.14232/phd.3926 UR - https://m2.mtmt.hu/api/publication/3267993 ID - 3267993 LA - Hungarian DB - MTMT ER -