TY - JOUR AU - Villegas, SN AU - Gombos, Rita I AU - Garcia-Lopez, L AU - Gutierrez-Perez, I AU - Garcia-Castillo, J AU - Vallejo, DM AU - Da, Ros VG AU - Ballesta-Illan, E AU - Mihály, József AU - Dominguez, M TI - PI3K/Akt Cooperates with Oncogenic Notch by Inducing Nitric Oxide-Dependent Inflammation JF - CELL REPORTS J2 - CELL REP VL - 22 PY - 2018 IS - 10 SP - 2541 EP - 2549 PG - 9 SN - 2211-1247 DO - 10.1016/j.celrep.2018.02.049 UR - https://m2.mtmt.hu/api/publication/3354869 ID - 3354869 N1 - WoS:hiba:000427081800004 2019-11-12 23:53 első szerző nem egyezik AB - The PI3K/Akt signaling pathway, Notch, and other oncogenes cooperate in the induction of aggressive cancers. Elucidating how the PI3K/Akt pathway facilitates tumorigenesis by other oncogenes may offer opportunities to develop drugs with fewer side effects than those currently available. Here, using an unbiased in vivo chemical genetic screen in Drosophila, we identified compounds that inhibit the activity of proinflammatory enzymes nitric oxide synthase (NOS) and lipoxygenase (LOX) as selective suppressors of Notch-PI3K/Akt cooperative oncogenesis. Tumor silencing of NOS and LOX signaling mirrored the antitumor effect of the hit compounds, demonstrating their participation in Notch-PI3K/Akt- induced tumorigenesis. Oncogenic PI3K/Akt signaling triggered inflammation and immunosuppression via aberrant NOS expression. Accordingly, activated Notch tumorigenesis was fueled by hampering the immune response or by NOS overexpression to mimic a protumorigenic environment. Our lead compound, the LOX inhibitor BW B70C, also selectively killed human leukemic cells by dampening the NOTCH1-PI3K/AKT-eNOS axis. LA - English DB - MTMT ER - TY - JOUR AU - Migh, Ede AU - Gotz, T AU - Földi, István AU - Szikora, Szilárd AU - Gombos, Rita I AU - Darula, Zsuzsanna AU - Medzihradszky F., Katalin AU - Maléth, József AU - Hegyi, Péter AU - Sigrist, S AU - Mihály, József TI - Microtubule organization in presynaptic boutons relies on the formin DAAM JF - DEVELOPMENT J2 - DEVELOPMENT VL - 145 ET - 0 PY - 2018 IS - 6 PG - 13 SN - 0950-1991 DO - 10.1242/dev.158519 UR - https://m2.mtmt.hu/api/publication/3343168 ID - 3343168 N1 - Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, MTA-SZBK NAP B Axon Growth and Regeneration Group, Temesvári krt. 62, Szeged, H-6726, Hungary Institut für Biologie/Genetik and NeuroCure, Freie Universitat Berlin, Takustrasse 6, Berlin, D-14195, Germany Laboratory of Proteomics Research, Biological Research Centre, Hungarian Academy of Sciences, Szeged, H-6726, Hungary MTA-SZTE Translational Gastroenterology Research Group, Szeged, H-6725, Hungary Institute for Translational Medicine, University of Pecs, Pécs, H-7624, Hungary Cited By :11 Export Date: 17 October 2023 CODEN: DEVPE Correspondence Address: Mihály, J.; Institute of Genetics, Temesvári krt. 62, Hungary; email: mihaly.jozsef@brc.mta.hu AB - Regulation of the cytoskeleton is fundamental to the development and functioning of synaptic terminals, such as neuromuscular junctions. Nevertheless, despite identification of numerous proteins that regulate synaptic actin and microtubule dynamics, the mechanisms of cytoskeletal control during terminal arbor formation has remained largely elusive. Here, we show that DAAM, a member of the formin family of cytoskeleton organizing factors, is an important presynaptic regulator of neuromuscular junction development in Drosophila We demonstrate that the actin filament assembly activity of DAAM plays a negligible role in terminal formation; rather, DAAM is necessary for synaptic microtubule organization. Genetic interaction studies consistently link DAAM with the Wg/Ank2/Futsch module of microtubule regulation and bouton formation. Finally, we provide evidence that DAAM is tightly associated with the synaptic active zone scaffold, and electrophysiological data point to a role in the modulation of synaptic vesicle release. Based on these results, we propose that DAAM is an important cytoskeletal effector element of the Wg/Ank2 pathway involved in the determination of basic synaptic structures, and, additionally, DAAM may couple the active zone scaffold to the presynaptic cytoskeleton. LA - English DB - MTMT ER - TY - JOUR AU - Földi, István AU - Szikora, Szilárd AU - Mihály, József TI - Formin’ bridges between microtubules and actin filaments in axonal growth cones JF - NEURAL REGENERATION RESEARCH J2 - NEUR REG RES VL - 12 PY - 2017 IS - 12 SP - 1971 EP - 1973 PG - 3 SN - 1673-5374 DO - 10.4103/1673-5374.221148 UR - https://m2.mtmt.hu/api/publication/3314386 ID - 3314386 N1 - Cited By :3 Export Date: 21 January 2021 Correspondence Address: Mihály, J.; Institute of Genetics, Hungary; email: mihaly.jozsef@brc.mta.hu LA - English DB - MTMT ER - TY - JOUR AU - Dollar, G AU - Gombos, Rita I AU - Barnett, AA AU - Sanchez, Hernandez D AU - Maung, SM AU - Mihály, József AU - Jenny, A TI - Unique and Overlapping Functions of Formins Frl and DAAM During Ommatidial Rotation and Neuronal Development in Drosophila. JF - GENETICS J2 - GENETICS VL - 202 PY - 2016 IS - 3 SP - 1135 EP - 1151 PG - 17 SN - 0016-6731 DO - 10.1534/genetics.115.181438 UR - https://m2.mtmt.hu/api/publication/3040810 ID - 3040810 N1 - Department of Developmental and Molecular Biology, Bronx, NY 10461, United States Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, United States Office for Subsidized Research Units, Hungarian Academy of Sciences (HAS), Budapest, H-1051, Hungary Institute of Genetics, Biological Research Centre, HAS, Szeged, H-6726, Hungary Cited By :4 Export Date: 21 January 2021 CODEN: GENTA Correspondence Address: Jenny, A.; Albert Einstein College of Medicine, Chanin 503, 1300 Morris Park Ave., United States; email: andreas.jenny@einstein.yu.edu AB - The noncanonical Frizzled/planar cell polarity (PCP) pathway regulates establishment of polarity within the plane of an epithelium to generate diversity of cell fates, asymmetric, but highly aligned structures, or to orchestrate the directional migration of cells during convergent extension during vertebrate gastrulation. In Drosophila, PCP signaling is essential to orient actin wing hairs and to align ommatidia in the eye, in part by coordinating the movement of groups of photoreceptor cells during ommatidial rotation. Importantly, the coordination of PCP signaling with changes in the cytoskeleton is essential for proper epithelial polarity. Formins polymerize linear actin filaments and are key regulators of the actin cytoskeleton. Here, we show that the diaphanous-related formin, Frl, the single fly member of the FMNL (formin related in leukocytes/formin-like) formin subfamily affects ommatidial rotation in the Drosophila eye and is controlled by the Rho family GTPase Cdc42. Interestingly, we also found that frl mutants exhibit an axon growth phenotype in the mushroom body, a center for olfactory learning in the Drosophila brain, which is also affected in a subset of PCP genes. Significantly, Frl cooperates with Cdc42 and another formin, DAAM, during mushroom body formation. This study thus suggests that different formins can cooperate or act independently in distinct tissues, likely integrating various signaling inputs with the regulation of the cytoskeleton. It furthermore highlights the importance and complexity of formin-dependent cytoskeletal regulation in multiple organs and developmental contexts. LA - English DB - MTMT ER - TY - JOUR AU - Hackler, L Jr AU - Ózsvári, Béla AU - Gyuris, M AU - Sipos, Péter AU - Fábián, Gabriella AU - Molnár, Eszter AU - Marton, Annamária AU - Faragó, Nóra AU - Mihály, József AU - Nagy, Lajos István AU - Szénási, Tibor AU - Diron, A AU - Párducz, Árpád AU - Kanizsai, Iván AU - Puskás, László TI - The Curcumin Analog C-150, Influencing NF-kappaB, UPR and Akt/Notch Pathways Has Potent Anticancer Activity In Vitro and In Vivo. JF - PLOS ONE J2 - PLOS ONE VL - 11 PY - 2016 IS - 3 PG - 16 SN - 1932-6203 DO - 10.1371/journal.pone.0149832 UR - https://m2.mtmt.hu/api/publication/3032868 ID - 3032868 N1 - AVIDIN Ltd., Szeged, Hungary Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary AVICOR Ltd., Szeged, Hungary Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary Institute of Biophysics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary Cited By :32 Export Date: 3 May 2022 CODEN: POLNC Chemicals/CAS: curcumin, 458-37-7; protein kinase B, 148640-14-6; Acrylamides; Antineoplastic Agents; C-150 curcumin; Curcumin; NF-kappa B; Proto-Oncogene Proteins c-akt; Receptors, Notch Tradenames: c 150 AB - C-150 a Mannich-type curcumin derivative, exhibited pronounced cytotoxic effects against eight glioma cell lines at micromolar concentrations. Inhibition of cell proliferation by C-150 was mediated by affecting multiple targets as confirmed at transcription and protein level. C-150 effectively reduced the transcription activation of NFkB, inhibited PKC-alpha which are constitutively over-expressed in glioblastoma. The effects of C-150 on the Akt/ Notch signaling were also demonstrated in a Drosophila tumorigenesis model. C-150 reduced the number of tumors in Drosophila with similar efficacy to mitoxantrone. In an in vivo orthotopic glioma model, C-150 significantly increased the median survival of treated nude rats compared to control animals. The multi-target action of C-150, and its preliminary in vivo efficacy would render this curcumin analogue as a potent clinical candidate against glioblastoma. LA - English DB - MTMT ER - TY - JOUR AU - Gombos, Rita I AU - Migh, Ede AU - Antal, Otilia Tamara AU - Mukherjee, A AU - Jenny, A AU - Mihály, József TI - The Formin DAAM Functions as Molecular Effector of the Planar Cell Polarity Pathway during Axonal Development in Drosophila JF - JOURNAL OF NEUROSCIENCE J2 - J NEUROSCI VL - 35 PY - 2015 IS - 28 SP - 10154 EP - 10167 PG - 14 SN - 0270-6474 DO - 10.1523/JNEUROSCI.3708-14.2015 UR - https://m2.mtmt.hu/api/publication/2931297 ID - 2931297 AB - Recent studies established that the planar cell polarity (PCP) pathway is critical for various aspects of nervous system development and function, including axonal guidance. Although it seems clear that PCP signaling regulates actin dynamics, the mechanisms through which this occurs remain elusive. Here, we establish a functional link between the PCP system and one specific actin regulator, the formin DAAM, which has previously been shown to be required for embryonic axonal morphogenesis and filopodia formation in the growth cone. We show that dDAAM also plays a pivotal role during axonal growth and guidance in the adult Drosophila mushroom body, a brain center for learning and memory. By using a combination of genetic and biochemical assays, we demonstrate that Wnt5 and the PCP signaling proteins Frizzled, Strabismus, and Dishevelled act in concert with the small GTPase Rac1 to activate the actin assembly functions of dDAAM essential for correct targeting of mushroom body axons. Collectively, these data suggest that dDAAM is used as a major molecular effector of the PCP guidance pathway. By uncovering a signaling system from the Wnt5 guidance cue to an actin assembly factor, we propose that the Wnt5/PCP navigation system is linked by dDAAM to the regulation of the growth cone actin cytoskeleton, and thereby growth cone behavior, in a direct way. LA - English DB - MTMT ER -