@article{MTMT:34175360,
	title = {Expression, Function and Trafficking of the Human ABCG2 Multidrug Transporter Containing Mutations in an Unstructured Cytoplasmic Loop},
	url = {https://m2.mtmt.hu/api/publication/34175360},
	author = {Mózner, Orsolya and Zámbó, Boglárka and Bartos, Zsuzsa and Gergely, Anna and Szabó, Kata Sára and Jezsó, Bálint and Telbisz, Ágnes Mária and Várady, György and Homolya, László and Hegedűs, Tamás and Sarkadi, Balázs},
	doi = {10.3390/membranes13100822},
	journal-iso = {MEMBRANES-BASEL},
	journal = {MEMBRANES (BASEL)},
	volume = {13},
	unique-id = {34175360},
	abstract = {The human ABCG2 multidrug transporter plays a crucial role in the absorption and excretion of xeno- and endobiotics, contributes to cancer drug resistance and the development of gout. In this work, we have analyzed the effects of selected variants, residing in a structurally unresolved cytoplasmic region (a.a. 354–367) of ABCG2 on the function and trafficking of this protein. A cluster of four lysines (K357–360) and the phosphorylation of a threonine (T362) residue in this region have been previously suggested to significantly affect the cellular fate of ABCG2. Here, we report that the naturally occurring K360del variant in human cells increased ABCG2 plasma membrane expression and accelerated cellular trafficking. The variable alanine replacements of the neighboring lysines had no significant effect on transport function, and the apical localization of ABCG2 in polarized cells has not been altered by any of these mutations. Moreover, in contrast to previous reports, we found that the phosphorylation-incompetent T362A, or the phosphorylation-mimicking T362E variants in this loop had no measurable effects on the function or expression of ABCG2. Molecular dynamics simulations indicated an increased mobility of the mutant variants with no major effects on the core structure of the protein. These results may help to decipher the potential role of this unstructured region within this transporter.},
	year = {2023},
	eissn = {2077-0375},
	orcid-numbers = {Mózner, Orsolya/0000-0001-5784-7702; Bartos, Zsuzsa/0000-0001-9695-1422; Jezsó, Bálint/0000-0002-1306-4797; Telbisz, Ágnes Mária/0000-0003-0972-4606; Várady, György/0000-0003-2012-9680; Homolya, László/0000-0003-1639-8140; Hegedűs, Tamás/0000-0002-0331-9629; Sarkadi, Balázs/0000-0003-0592-4539}
}

@article{MTMT:33061607,
	title = {Genetic polymorphisms and decreased protein expression of ABCG2 urate transporters are associated with susceptibility to gout, disease severity and renal-overload hyperuricemia},
	url = {https://m2.mtmt.hu/api/publication/33061607},
	author = {Pálinkás, Márton and Szabó, Edit Zsuzsanna and Kulin, Anna and Mózner, Orsolya and Rásonyi, R. and Juhász, Péter and Nagy, K. and Várady, György and Vörös, D. and Zámbó, Boglárka and Sarkadi, Balázs and Poór, Gyula},
	doi = {10.1007/s10238-022-00848-7},
	journal-iso = {CLIN EXP MED},
	journal = {CLINICAL AND EXPERIMENTAL MEDICINE},
	volume = {23},
	unique-id = {33061607},
	issn = {1591-8890},
	abstract = {Gout is a common crystal induced disease of high personal and social burden, characterised by severe arthritis and comorbidity if untreated. Impaired function of ABCG2 transporter is causative in gout and may be responsible for renal-overload type hyperuricemia. Despite its importance, there is limited information on how clinical parameters correlate with protein expression and that with genetic changes. Urate and clinical parameters of 78 gouty patients and healthy controls were measured among standardised circumstances from a Hungarian population. ABCG2 membrane expression of red blood cells was determined by flow cytometry-based method and SNPs of this protein were analysed by TaqMan-based qPCR. The prevalence of ABCG2 functional polymorphisms in gouty and control patients were 32.1 and 13.7%, respectively. Most common SNP was Q141K while one sample with R236X, R383C and the lately described M71V were found in the gouty population. These polymorphisms showed strong linkage with decreased protein expression while the latter was also associated with higher fractional urate excretion (FUE) and urinary urate excretion (UUE). This study firstly evaluated ABCG2 protein expression in a clinically defined gouty population while also proving its associations between ABCG2 genetic changes and renal-overload hyperuricemia. The paper also highlighted relations between ABCG2 SNPs, gout susceptibility and disease severity characterised by an early onset disease with frequent flares and tophi formation.},
	year = {2023},
	eissn = {1591-9528},
	pages = {1277-1284},
	orcid-numbers = {Kulin, Anna/0000-0002-2877-5831; Mózner, Orsolya/0000-0001-5784-7702; Várady, György/0000-0003-2012-9680; Sarkadi, Balázs/0000-0003-0592-4539; Poór, Gyula/0000-0001-9235-3900}
}

@article{MTMT:32156982,
	title = {Modulation of the Human Erythroid Plasma Membrane Calcium Pump (PMCA4b) Expression by Polymorphic Genetic Variants},
	url = {https://m2.mtmt.hu/api/publication/32156982},
	author = {Mózner, Orsolya and Zámbó, Boglárka and Sarkadi, Balázs},
	doi = {10.3390/membranes11080586},
	journal-iso = {MEMBRANES-BASEL},
	journal = {MEMBRANES (BASEL)},
	volume = {11},
	unique-id = {32156982},
	abstract = {In the human ATP2B4 gene, coding for the plasma membrane calcium pump PMCA4b, a minor haplotype results in the decreased expression of this membrane protein in erythroid cells. The presence of this haplotype and the consequently reduced PMCA4b expression have been suggested to affect red blood cell hydration and malaria susceptibility. By using dual-luciferase reporter assays, we have localized the erythroid-specific regulatory region within the haplotype of the ATP2B4 gene, containing predicted GATA1 binding sites that are affected by SNPs in the minor haplotype. Our results show that, in human erythroid cells, the regulation of ATP2B4 gene expression is significantly affected by GATA1 expression, and we document the role of specific SNPs involved in predicted GATA1 binding. Our findings provide a mechanistic explanation at the molecular level for the reduced erythroid-specific PMCA4b expression in carriers of ATP2B4 gene polymorphic variants.},
	year = {2021},
	eissn = {2077-0375},
	orcid-numbers = {Mózner, Orsolya/0000-0001-5784-7702; Sarkadi, Balázs/0000-0003-0592-4539}
}

@article{MTMT:30924863,
	title = {Molecular Diversity of Plasma Membrane Ca2+ Transporting ATPases: Their Function Under Normal and Pathological Conditions},
	url = {https://m2.mtmt.hu/api/publication/30924863},
	author = {Hegedűs, L. and Zámbó, Boglárka and Pászty, Katalin and Padányi, Rita and Varga, Karolina and Penniston, J.T. and Enyedi, Ágnes},
	doi = {10.1007/978-3-030-12457-1_5},
	journal-iso = {ADV EXP MED BIOL},
	journal = {ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY},
	volume = {1131},
	unique-id = {30924863},
	issn = {0065-2598},
	abstract = {Plasma membrane Ca2+ transport ATPases (PMCA1-4, ATP2B1-4) are responsible for removing excess Ca2+ from the cell in order to keep the cytosolic Ca2+ ion concentration at the low level essential for normal cell function. While these pumps take care of cellular Ca2+ homeostasis they also change the duration and amplitude of the Ca2+ signal and can create Ca2+ gradients across the cell. This is accomplished by generating more than twenty PMCA variants each having the character – fast or slow response, long or short memory, distinct interaction partners and localization signals – that meets the specific needs of the particular cell-type in which they are expressed. It has become apparent that these pumps are essential to normal tissue development and their malfunctioning can be linked to different pathological conditions such as certain types of neurodegenerative and heart diseases, hearing loss and cancer. In this chapter we summarize the complexity of PMCA regulation and function under normal and pathological conditions with particular attention to recent developments of the field. © Springer Nature Switzerland AG 2020.},
	keywords = {Animals; Humans; metabolism; GENETICS; CALMODULIN; human; animal; physiology; Cell Membrane; pathology; enzymology; Homeostasis; Genetic Variation; Cytosol; actin cytoskeleton; Plasma Membrane Calcium-Transporting ATPases; plasma membrane calcium transporting adenosine triphosphatase; ALTERED EXPRESSION; Ca2+ signal; Alternative splice; ATP2B1-4; Pathological condition; Phosphatidylinositol-45-bisphosphate; Plasma membrane Ca2+ ATPase (PMCA)},
	year = {2020},
	eissn = {2214-8019},
	pages = {93-129},
	orcid-numbers = {Pászty, Katalin/0000-0003-2457-8555; Padányi, Rita/0000-0001-7798-0463; Varga, Karolina/0000-0003-4746-8738; Enyedi, Ágnes/0000-0002-7366-9376}
}

@article{MTMT:31240593,
	title = {Precision-engineered reporter cell lines reveal ABCG2 regulation in live lung cancer cells},
	url = {https://m2.mtmt.hu/api/publication/31240593},
	author = {Kovacsics, Daniella and Brózik, Anna and Tihanyi, Borbála and Matula, Zsolt and Borsy, Adrienn and Mészáros, Nikolett and Szabó, Edit Zsuzsanna and Németh, Eszter and Fóthi, Ábel and Zámbó, Boglárka and Szüts, Dávid and Várady, György and Orbán, Tamás I. and Apáti, Ágota and Sarkadi, Balázs},
	doi = {10.1016/j.bcp.2020.113865},
	journal-iso = {BIOCHEMIC PHARMACOL},
	journal = {BIOCHEMICAL PHARMACOLOGY},
	volume = {175},
	unique-id = {31240593},
	issn = {0006-2952},
	abstract = {Expression of the ABCG2 multidrug transporter is a marker of cancer stem cells and a predictor of recurrent malignant disease. Understanding how human ABCG2 expression is modulated by pharmacotherapy is crucial in guiding therapeutic recommendations and may aid rational drug development. Genome edited reporter cells are useful in investigating gene regulation and visualizing protein activity in live cells but require precise targeting to preserve native regulatory regions. Here, we describe a fluorescent reporter assay that allows the noninvasive assessment of ABCG2 regulation in human lung adenocarcinoma cells. Using CRISPR-Cas9 gene editing coupled with homology-directed repair, we targeted an eGFP coding sequence to the translational start site of ABCG2, generating ABCG2 knock-out and in situ tagged ABCG2 reporter cells. Using the engineered cell lines, we show that ABCG2 is upregulated by a number of anti-cancer medications, HDAC inhibitors, hypoxia-mimicking agents and glucocorticoids, supporting a model in which ABCG2 is under the control of a general stress response. To our knowledge, this is the first description of a fluorescent reporter assay system designed to follow the endogenous regulation of a human ABC transporter in live cells. The information gained may guide therapy recommendations and aid rational drug design.},
	keywords = {GLUCOCORTICOIDS; lung cancer; CRISPR-Cas9; Reporter cell lines; ABCG2 regulation},
	year = {2020},
	eissn = {1873-2968},
	orcid-numbers = {Várady, György/0000-0003-2012-9680; Orbán, Tamás I./0000-0002-3424-3428; Sarkadi, Balázs/0000-0003-0592-4539}
}

@article{MTMT:30745945,
	title = {Cellular expression and function of naturally occurring variants of the human ABCG2 multidrug transporter},
	url = {https://m2.mtmt.hu/api/publication/30745945},
	author = {Zámbó, Boglárka and Mózner, Orsolya and Bartos, Zsuzsa and Török, György and Várady, György and Telbisz, Ágnes Mária and Homolya, László and Orbán, Tamás I. and Sarkadi, Balázs},
	doi = {10.1007/s00018-019-03186-2},
	journal-iso = {CELL MOL LIFE SCI},
	journal = {CELLULAR AND MOLECULAR LIFE SCIENCES},
	volume = {77},
	unique-id = {30745945},
	issn = {1420-682X},
	abstract = {The human ABCG2 multidrug transporter plays a crucial role in the absorption and excretion of xeno- and endobiotics; thus the relatively frequent polymorphic and mutant ABCG2 variants in the population may significantly alter disease conditions and pharmacological effects. Low-level or non-functional ABCG2 expression may increase individual drug toxicity, reduce cancer drug resistance, and result in hyperuricemia and gout. In the present work we have studied the cellular expression, trafficking, and function of nine naturally occurring polymorphic and mutant variants of ABCG2. A comprehensive analysis of the membrane localization, transport, and ATPase activity, as well as retention and degradation in intracellular compartments was performed. Among the examined variants, R147W and R383C showed expression and/or protein folding defects, indicating that they could indeed contribute to ABCG2 functional deficiency. These studies and the applied methods should significantly promote the exploration of the medical effects of these personal variants, promote potential therapies, and help to elucidate the specific role of the affected regions in the folding and function of the ABCG2 protein. © 2019, The Author(s).},
	keywords = {ABCG2; BCRP; membrane transporter; MXR; natural variants},
	year = {2020},
	eissn = {1420-9071},
	pages = {365-378},
	orcid-numbers = {Mózner, Orsolya/0000-0001-5784-7702; Bartos, Zsuzsa/0000-0001-9695-1422; Török, György/0000-0001-7616-5782; Várady, György/0000-0003-2012-9680; Telbisz, Ágnes Mária/0000-0003-0972-4606; Homolya, László/0000-0003-1639-8140; Orbán, Tamás I./0000-0002-3424-3428; Sarkadi, Balázs/0000-0003-0592-4539}
}

@article{MTMT:30924895,
	title = {Cellular Processing of the ABCG2 Transporter-Potential Effects on Gout and Drug Metabolism.},
	url = {https://m2.mtmt.hu/api/publication/30924895},
	author = {Mózner, Orsolya and Bartos, Zsuzsa and Zámbó, Boglárka and Homolya, László and Hegedűs, Tamás and Sarkadi, Balázs},
	doi = {10.3390/cells8101215},
	journal-iso = {CELLS-BASEL},
	journal = {CELLS},
	volume = {8},
	unique-id = {30924895},
	abstract = {The human ABCG2 is an important plasma membrane multidrug transporter, involved in uric acid secretion, modulation of absorption of drugs, and in drug resistance of cancer cells. Variants of the ABCG2 transporter, affecting cellular processing and trafficking, have been shown to cause gout and increased drug toxicity. In this paper, we overview the key cellular pathways involved in the processing and trafficking of large membrane proteins, focusing on ABC transporters. We discuss the information available for disease-causing polymorphic variants and selected mutations of ABCG2, causing increased degradation and impaired travelling of the transporter to the plasma membrane. In addition, we provide a detailed in silico analysis of an as yet unrecognized loop region of the ABCG2 protein, in which a recently discovered mutation may actually promote ABCG2 membrane expression. We suggest that post-translational modifications in this unstructured loop at the cytoplasmic surface of the protein may have special influence on ABCG2 processing and trafficking.},
	keywords = {drug metabolism; gout; ABC TRANSPORTERS; ABCG2 multidrug transporter; ABCG2 trafficking},
	year = {2019},
	eissn = {2073-4409},
	orcid-numbers = {Mózner, Orsolya/0000-0001-5784-7702; Bartos, Zsuzsa/0000-0001-9695-1422; Homolya, László/0000-0003-1639-8140; Hegedűs, Tamás/0000-0002-0331-9629; Sarkadi, Balázs/0000-0003-0592-4539}
}

@article{MTMT:31432864,
	title = {Potential Diagnostic Application of the Quantitative Assessment of Red Blood Cell Membrane Protein Expression},
	url = {https://m2.mtmt.hu/api/publication/31432864},
	author = {Várady, György and Szabó, Edit Zsuzsanna and Kulin, Anna and Zámbó, Boglárka and Mózner, Orsolya and Pálinkás, Márton and Poór, Gyula and Sarkadi, Balázs},
	journal-iso = {THROMBOSIS HAEMOSTASIS RES},
	journal = {THROMBOSIS AND HAEMOSTASIS: RESEARCH},
	volume = {3},
	unique-id = {31432864},
	year = {2019},
	eissn = {2689-9663},
	orcid-numbers = {Várady, György/0000-0003-2012-9680; Kulin, Anna/0000-0002-2877-5831; Mózner, Orsolya/0000-0001-5784-7702; Poór, Gyula/0000-0001-9235-3900; Sarkadi, Balázs/0000-0003-0592-4539}
}

@mastersthesis{MTMT:30764866,
	title = {Membránfehérjék vizsgálata vörösvértesteken, a kapcsolódó genetikai variánsok azonosítása és jellemzése},
	url = {https://m2.mtmt.hu/api/publication/30764866},
	author = {Zámbó, Boglárka},
	doi = {10.14753/SE.2019.2259},
	unique-id = {30764866},
	year = {2019}
}

@article{MTMT:3370208,
	title = {Clinically relevant mutations in the ABCG2 transporter uncovered by genetic analysis linked to erythrocyte membrane protein expression},
	url = {https://m2.mtmt.hu/api/publication/3370208},
	author = {Zámbó, Boglárka and Bartos, Zsuzsa and Mózner, Orsolya and Szabó, Edit Zsuzsanna and Várady, György and Poór, Gyula and Pálinkás, Márton and Andrikovics, Hajnalka and Hegedűs, Tamás and Homolya, László and Sarkadi, Balázs},
	doi = {10.1038/s41598-018-25695-z},
	journal-iso = {SCI REP},
	journal = {SCIENTIFIC REPORTS},
	volume = {8},
	unique-id = {3370208},
	abstract = {The ABCG2 membrane protein is a key xeno- and endobiotic transporter, modulating the absorption and metabolism of pharmacological agents and causing multidrug resistance in cancer. ABCG2 is also involved in uric acid elimination and its impaired function is causative in gout. Analysis of ABCG2 expression in the erythrocyte membranes of healthy volunteers and gout patients showed an enrichment of lower expression levels in the patients. By genetic screening based on protein expression, we found a relatively frequent, novel ABCG2 mutation (ABCG2-M71V), which, according to cellular expression studies, causes reduced protein expression, although with preserved transporter capability. Molecular dynamics simulations indicated a stumbled dynamics of the mutant protein, while ABCG2-M71V expression in vitro could be corrected by therapeutically relevant small molecules. These results suggest that personalized medicine should consider this newly discovered ABCG2 mutation, and genetic analysis linked to protein expression provides a new tool to uncover clinically important mutations in membrane proteins. © 2018 The Author(s).},
	year = {2018},
	eissn = {2045-2322},
	orcid-numbers = {Bartos, Zsuzsa/0000-0001-9695-1422; Mózner, Orsolya/0000-0001-5784-7702; Várady, György/0000-0003-2012-9680; Poór, Gyula/0000-0001-9235-3900; Hegedűs, Tamás/0000-0002-0331-9629; Homolya, László/0000-0003-1639-8140; Sarkadi, Balázs/0000-0003-0592-4539}
}