Szerző szerinti böngészés "Fadel, Lina"

Megjelenítve 1 - 5 (Összesen 5)
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    Agonist binding directs dynamic competition among nuclear receptors for heterodimerization with their common partner, retinoid X receptor
    Fadel, Lina; Vámosi, György; Molekuláris orvostudomány doktori iskola; DE--Mezőgazdaság- Élelmiszertudományi és Környezetgazdálkodási Kar -- Biofizikai és Sejtbiológiai Intézet; DE--Mezőgazdaság- Élelmiszertudományi és Környezetgazdálkodási Kar -- Biofizikai és Sejtbiológiai Intézet
    Tracing the dynamic distribution pattern of EGFP-VDR, EGFP-PPAR/nlsm and EGFP-RARα/nlsm (homogeneous in the absence of RXRα and nuclear-enriched in response to RXRα binding) serves as a good model system for studying their competition for heterodimerization with RXRα. There is indeed dynamic competition between RXR partners, which is governed by two mechanisms. First, in the absence of agonist treatment, there is a hierarchy of affinities between RXRα and its partners in the following order: RARα > PPARγ > VDR. Second, in the presence of agonist treatment, RXRα partner selection is shifted towards the liganded partner. Our results also show that RXR-NR heterodimerization and direct DNA binding are correlated events, and both are augmented by agonist treatment. These results may explain certain side effects of drugs targeting NRs. Competition for RXR could be responsible for the symptoms of vitamin D deficiency developed in a child upon receiving systemic retinoid treatment for ichthyosis188, or the antagonistic effect of co-administered vitamin A on serum calcium response to vitamin D treatment189. Our observations regarding these three RXR partners, consistently with metabolism regulation by two other RXR partners (LXR and PPARα) and similar previous findings on membrane-localized IL-2/15 receptors encourage us to generalize the concept that specific ligand binding may often govern competition between different partners of a promiscuous receptor. Our findings are a proof-of-concept of a hierarchy of affinities between NRs and their common partner, RXRα. These studies can be extended to a larger number of receptors to uncover the network of hierarchies, and follow-up studies will also be focusing on testing this concept in a broader and physiological context. It is worth to mention that our or similar studies may have some limitations: i) we cannot entirely exclude the presence of endogenous ligands for the receptors; and ii) our approach may not mimic all possible physiological conditions; iii) as for the limiting nature of RXR, antibody-based approaches are at best semiquantitative to determine endogenous NR concentrations; iv) finally, we used indirect measures to assess downstream gene expression events.
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    Agonist-controlled competition of RAR and VDR nuclear receptors for heterodimerization with RXR is manifested in their DNA-binding
    (2023) Rehó, Bálint; Fadel, Lina; Brázda, Péter; Benziane, Anass; Hegedűs, Éva; Sen, Pialy; Gadella, Theodorus W.; Tóth, Katalin; Nagy, László; Vámosi, György
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    Doxorubicin impacts chromatin binding of HMGB1, Histone H1 and retinoic acid receptor
    (2022) Bosire, Rosevalentine; Fadel, Lina; Mocsár, Gábor; Nánási, Péter Pál ifj.; Sen, Pialy; Sharma, Anshu Kumar; Naseem, Muhammad Umair; Kovács, Attila; Kugel, Jennifer; Kroemer, Guido; Vámosi, György; Szabó, Gábor
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    EGR2 is an epigenomic regulator of phagocytosis and antifungal immunity in alveolar macrophages
    (2024) Kolostyák, Zsuzsanna; Bojcsuk, Dóra; Baksa, Viktória; Máthéné Szigeti, Zsuzsa; Bene, Krisztián; Czimmerer, Zsolt; Botó, Pál; Fadel, Lina; Póliska, Szilárd; Halász, László; Tzerpos, Petros; Berger, Wilhelm K.; Villabona-Rueda, Andres; Varga, Zsófia; Kovács, Tünde; Patsalos, Andreas; Pap, Attila; Vámosi, György; Bai, Péter; Dezső, Balázs; Spite, Matthew; D'Alessio,, Franco R.; Szatmári, István; Nagy, László
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    The effect of Doxorubicin on the nuclear mobility of retinoic acid receptor
    Sharma, Anshu Kumar; Fadel, Lina; Vámosi, György; DE--Természettudományi és Technológiai Kar--Biotechnológiai Intézet
    Nuclear receptors are transcription factors regulating the transcription of their target genes in a ligand-dependent manner. They regulate a series of cellular processes including cell growth, differentiation, metabolism, cell death, and immune responses. NRs like retinoic acid receptors (RAR) requires heterodimerization with retinoid X receptors (RXR) for proper transcriptional activity. These receptors diffuse in the nucleus and bind to chromatin even non-specifically or specifically; binding to their hormone response elements. Doxorubicin (Dox) is an anti-cancer drug used as a medicine e.g., for bladder, breast, stomach, soft tissue sarcoma, multiple myeloma cancers. Dox molecules intercalate between DNA bases and thereby inhibit topoisomerase II activity interfering with the transcription process. Dox treatment has many side effects mainly, Dox-induced cardiotoxicity (DIC). Because it rearranges the chromatin, it may interfere with the function of transcription factors. FRAP was used to clarify the impact of dox treatment on the DNA binding properties of RAR. It was observed that dox increased the average mobility of RAR; it decreased the total DNA binding of RAR as indicated by the reduction in τaverage . Interestingly the specific binding of RAR was enhanced in a dose-dependent manner; indicated by the increase in slow fraction and immobile fraction. The reduction of RAR binding induced by Dox may explain the DIC. It could also support the proposal (Dox and retinoic acid) co-treatment strategies applied to augment antitumor and ameliorate side effects.