@article{MTMT:34050718,
	title = {The Nuclear Localization Signal of NF-κB p50 Enters the Cells via Syndecan-Mediated Endocytosis and Inhibits NF-κB Activity},
	url = {https://m2.mtmt.hu/api/publication/34050718},
	author = {Letoha, Annamária and Hudák, Anett and Bozsó, Zsolt and Vizler, Csaba and Veres, Gábor and Szilák, László and Letoha, Tamás},
	doi = {10.1007/s10989-023-10548-9},
	journal-iso = {INT J PEPT RES THER},
	journal = {INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS},
	volume = {29},
	unique-id = {34050718},
	issn = {1573-3149},
	abstract = {It is well established that cationic peptides can enter cells following attachment to polyanionic membrane components. We report that the basic nuclear localization signal (NLS) of the NF-κB p50 subunit is internalized via lipid raft-dependent endocytosis mediated by heparan sulfate proteoglycans and exerts significant NF-κB inhibitory activities both in vitro and in vivo. In vitro uptake experiments revealed that the p50 NLS peptide (CYVQRKRQKLMP) enters the cytoplasm and accumulates in the nucleus at 37 °C. Depleting cellular ATP pools or decreasing temperature to 4 °C abolished peptide internalization, confirming the active, energy-dependent endocytic uptake. Co-incubation with heparan sulfate or replacing the peptide’s basic residues with glycines markedly reduced the intracellular entry of the p50 NLS, referring to the role of polyanionic cell-surface proteoglycans in internalization. Furthermore, treatment with methyl-β-cyclodextrin greatly inhibited the peptide’s membrane translocation. Overexpression of the isoforms of the syndecan family of transmembrane proteoglycans, especially syndecan-4, increased the cellular internalization of the NLS, suggesting syndecans’ involvement in the peptide’s cellular uptake. In vitro , p50 NLS reduced NF-κB activity in TNF-α-induced L929 fibroblasts and LPS-stimulated RAW 264.7 macrophages. TNF-α-induced ICAM-1 expression of HMEC-1 human endothelial cells could also be inhibited by the peptide. Fifteen minutes after its intraperitoneal injection, the peptide rapidly entered the cells of the pancreas, an organ with marked syndecan-4 expression. In an acute pancreatitis model, an inflammatory disorder triggered by the activation of stress-responsive transcription factors like NF-κB, administration of the p50 NLS peptide reduced the severity of pancreatic inflammation by blocking NF-κB transcription activity and ameliorating the examined laboratory and histological markers of pancreatitis.},
	year = {2023},
	eissn = {1573-3904},
	orcid-numbers = {Bozsó, Zsolt/0000-0002-5713-3096}
}

@article{MTMT:33846356,
	title = {Reconsidering Dogmas about the Growth of Bacterial Populations},
	url = {https://m2.mtmt.hu/api/publication/33846356},
	author = {Ughy, Bettina and Nagyapáti, Sarolta and Lajkó, Dézi Bianka and Letoha, Tamas and Prohaszka, Adam and Deeb, Dima and Dér, András and Pettkó-Szandtner, Aladár and Szilák, László},
	doi = {10.3390/cells12101430},
	journal-iso = {CELLS-BASEL},
	journal = {CELLS},
	volume = {12},
	unique-id = {33846356},
	abstract = {The growth of bacterial populations has been described as a dynamic process of continuous reproduction and cell death. However, this is far from the reality. In a well fed, growing bacterial population, the stationary phase inevitably occurs, and it is not due to accumulated toxins or cell death. A population spends the most time in the stationary phase, where the phenotype of the cells alters from the proliferating ones, and only the colony forming unit (CFU) decreases after a while, not the total cell concentration. A bacterial population can be considered as a virtual tissue as a result of a specific differentiation process, in which the exponential-phase cells develop to stationary-phase cells and eventually reach the unculturable form. The richness of the nutrient had no effect on growth rate or on stationary cell density. The generation time seems not to be a constant value, but it depended on the concentration of the starter cultures. Inoculations with serial dilutions of stationary populations reveal a so-called minimal stationary cell concentration (MSCC) point, up to which the cell concentrations remain constant upon dilutions; that seems to be universal among unicellular organisms.},
	year = {2023},
	eissn = {2073-4409},
	orcid-numbers = {Letoha, Tamas/0000-0002-6035-4009; Prohaszka, Adam/0000-0002-2390-2387}
}

@article{MTMT:33630992,
	title = {Syndecan-4 Mediates the Cellular Entry of Adeno-Associated Virus 9},
	url = {https://m2.mtmt.hu/api/publication/33630992},
	author = {Hudák, Anett and Roach, Matthew and Pusztai, Dávid and Pettkó-Szandtner, Aladár and Letoha, Annamária and Szilák, László and Azzouz, Mimoun and Letoha, Tamás},
	doi = {10.3390/ijms24043141},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {33630992},
	issn = {1661-6596},
	abstract = {Due to their low pathogenicity, immunogenicity, and long-term gene expression, adeno-associated virus (AAV) vectors emerged as safe and efficient gene delivery tools, over-coming setbacks experienced with other viral gene delivery systems in early gene therapy trials. Among AAVs, AAV9 can translocate through the blood-brain barrier (BBB), making it a promising gene delivery tool for transducing the central nervous system (CNS) via systemic administration. Recent reports on the shortcomings of AAV9-mediated gene delivery into the CNS require reviewing the molecular base of AAV9 cellular biology. A more detailed understanding of AAV9’s cellular entry would eradicate current hurdles and enable more efficient AAV9-based gene therapy approaches. Syndecans, the transmembrane family of heparan-sulfate proteoglycans, facilitate the cellular uptake of various viruses and drug delivery systems. Utilizing human cell lines and syndecan-specific cellular assays, we assessed the involvement of syndecans in AAV9’s cellular entry. The ubiquitously expressed isoform, syndecan-4 proved its superiority in facilitating AAV9 internalization among syndecans. Introducing syndecan-4 into poorly transducible cell lines enabled robust AAV9-dependent gene transduction, while its knockdown reduced AAV9’s cellular entry. Attachment of AAV9 to syndecan-4 is mediated not just by the polyanionic heparan-sulfate chains but also by the cell-binding domain of the extracellular syndecan-4 core protein. Co-immunoprecipitation assays and affinity proteomics also confirmed the role of syndecan-4 in the cellular entry of AAV9. Overall, our findings highlight the universally expressed syndecan-4 as a significant contributor to the cellular internalization of AAV9 and provide a molecular-based, rational explanation for the low gene delivery potential of AAV9 into the CNS.},
	year = {2023},
	eissn = {1422-0067},
	orcid-numbers = {Letoha, Tamás/0000-0002-6035-4009}
}

@article{MTMT:33050457,
	title = {Biodistribution and Cellular Internalization of Inactivated SARS-CoV-2 in Wild-Type Mice},
	url = {https://m2.mtmt.hu/api/publication/33050457},
	author = {Hudak, Anett and Morgan, Gareth and Bacovsky, Jaromir and Patai, Roland and Polgár, Tamás Ferenc and Letoha, Annamaria and Pettkó-Szandtner, Aladár and Vizler, Csaba and Szilák, László and Letoha, Tamás},
	doi = {10.3390/ijms23147609},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {23},
	unique-id = {33050457},
	issn = {1661-6596},
	abstract = {Despite the growing list of identified SARS-CoV-2 receptors, the human angiotensin-converting enzyme 2 (ACE2) is still viewed as the main cell entry receptor mediating SARS-CoV-2 internalization. It has been reported that wild-type mice, like other rodent species of the Muridae family, cannot be infected with SARS-CoV-2 due to differences in their ACE2 receptors. On the other hand, the consensus heparin-binding motif of SARS-CoV-2's spike protein, PRRAR, enables the attachment to rodent heparan sulfate proteoglycans (HSPGs), including syndecans, a transmembrane HSPG family with a well-established role in clathrin- and caveolin-independent endocytosis. As mammalian syndecans possess a relatively conserved structure, we analyzed the cellular uptake of inactivated SARS-CoV-2 particles in in vitro and in vivo mice models. Cellular studies revealed efficient uptake into murine cell lines with established syndecan-4 expression. After intravenous administration, inactivated SARS-CoV-2 was taken up by several organs in vivo and could also be detected in the brain. Internalized by various tissues, inactivated SARS-CoV-2 raised tissue TNF-alpha levels, especially in the heart, reflecting the onset of inflammation. Our studies on in vitro and in vivo mice models thus shed light on unknown details of SARS-CoV-2 internalization and help broaden the understanding of the molecular interactions of SARS-CoV-2.},
	keywords = {MECHANISMS; PROTEIN; MEMBRANE; IMMUNODEFICIENCY-VIRUS TYPE-1; ENDOCYTOSIS; Proteoglycans; Heparan Sulfate Proteoglycans; CELLULAR UPTAKE; Syndecans; Syndecans; Biochemistry & Molecular Biology; COVID-19; SARS-CoV-2; ARGININE-RICH PEPTIDES},
	year = {2022},
	eissn = {1422-0067},
	orcid-numbers = {Letoha, Tamás/0000-0002-6035-4009}
}

@article{MTMT:32599003,
	title = {Syndecan-4 Is a Key Facilitator of the SARS-CoV-2 Delta Variant’s Superior Transmission},
	url = {https://m2.mtmt.hu/api/publication/32599003},
	author = {Hudák, Anett and Veres, Gábor and Letoha, Annamária and Szilák, László and Letoha, Tamás},
	doi = {10.3390/ijms23020796},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {23},
	unique-id = {32599003},
	issn = {1661-6596},
	year = {2022},
	eissn = {1422-0067},
	orcid-numbers = {Veres, Gábor/0000-0003-4413-779X; Letoha, Tamás/0000-0002-6035-4009}
}

@article{MTMT:32823174,
	title = {Salt Stress Induces Paramylon Accumulation and Fine-Tuning of the Macro-Organization of Thylakoid Membranes in Euglena gracilis Cells},
	url = {https://m2.mtmt.hu/api/publication/32823174},
	author = {Kanna, Sai Divya and Racskóné Domonkos, Ildikó and Kóbori, T.O. and Dergez, Ágnes Karolina and Böde, Kinga and Nagyapáti, Sarolta and Zsíros, Ottó and Ünnep, Renáta and Nagy, Gergely and Garab, Győző and Szilák, László and Solymosi, Katalin and Kovács, László and Ughy, Bettina},
	doi = {10.3389/fpls.2021.725699},
	journal-iso = {FRONT PLANT SCI},
	journal = {FRONTIERS IN PLANT SCIENCE},
	volume = {12},
	unique-id = {32823174},
	issn = {1664-462X},
	year = {2021},
	eissn = {1664-462X},
	orcid-numbers = {Solymosi, Katalin/0000-0001-5246-2547}
}

@article{MTMT:32106321,
	title = {The Interplay of Apoes with Syndecans in Influencing Key Cellular Events of Amyloid Pathology},
	url = {https://m2.mtmt.hu/api/publication/32106321},
	author = {Hudak, Anett and Jósvay, Katalin and Racskóné Domonkos, Ildikó and Letoha, Annamária and Szilák, László and Letoha, Tamás},
	doi = {10.3390/ijms22137070},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {22},
	unique-id = {32106321},
	issn = {1661-6596},
	abstract = {Apolipoprotein E (ApoE) isoforms exert intricate effects on cellular physiology beyond lipid transport and metabolism. ApoEs influence the onset of Alzheimer's disease (AD) in an isoform-dependent manner: ApoE4 increases AD risk, while ApoE2 decreases it. Previously we demonstrated that syndecans, a transmembrane proteoglycan family with increased expression in AD, trigger the aggregation and modulate the cellular uptake of amyloid beta (A beta). Utilizing our previously established syndecan-overexpressing cellular assays, we now explore how the interplay of ApoEs with syndecans contributes to key events, namely uptake and aggregation, in A beta pathology. The interaction of ApoEs with syndecans indicates isoform-specific characteristics arising beyond the frequently studied ApoE-heparan sulfate interactions. Syndecans, and among them the neuronal syndecan-3, increased the cellular uptake of ApoEs, especially ApoE2 and ApoE3, while ApoEs exerted opposing effects on syndecan-3-mediated A beta uptake and aggregation. ApoE2 increased the cellular internalization of monomeric A beta, hence preventing its extracellular aggregation, while ApoE4 decreased it, thus helping the buildup of extracellular plaques. The contrary effects of ApoE2 and ApoE4 remained once A beta aggregated: while ApoE2 reduced the uptake of A beta aggregates, ApoE4 facilitated it. Fibrillation studies also revealed ApoE4 ' s tendency to form fibrillar aggregates. Our results uncover yet unknown details of ApoE cellular biology and deepen our molecular understanding of the ApoE-dependent mechanism of A beta pathology.},
	keywords = {BINDING; ALZHEIMERS-DISEASE; IN-VITRO; ENDOCYTOSIS; SURFACE; Syndecans; protein aggregation; APOE; Biochemistry & Molecular Biology; amyloid beta; SH-SY5Y CELLS; HEPARAN-SULFATE PROTEOGLYCANS; GLAND EPITHELIAL-CELLS; APOLIPOPROTEIN-E ISOFORMS; 6-O-SULFATION},
	year = {2021},
	eissn = {1422-0067},
	orcid-numbers = {Letoha, Tamás/0000-0002-6035-4009}
}

@article{MTMT:31945022,
	title = {Overexpression of Human Syndecan-1 Protects against the Diethylnitrosamine-Induced Hepatocarcinogenesis in Mice},
	url = {https://m2.mtmt.hu/api/publication/31945022},
	author = {Reszegi, Andrea and Karászi, Katalin and Tóth, Gábor and Rada, Kristóf Róbert and Váncza, Lóránd and Turiák, Lilla and Schaff, Zsuzsa and Kiss, András and Szilák, László and Szabó, Gábor and Petővári, Gábor and Sebestyén, Anna and Dezső, Katalin and Regős, Eszter and Tátrai, Péter and Baghy, Kornélia and Kovalszky, Ilona},
	doi = {10.3390/cancers13071548},
	journal-iso = {CANCERS},
	journal = {CANCERS},
	volume = {13},
	unique-id = {31945022},
	year = {2021},
	eissn = {2072-6694},
	orcid-numbers = {Reszegi, Andrea/0000-0001-6902-7883; Tóth, Gábor/0000-0003-1428-7906; Rada, Kristóf Róbert/0000-0001-7849-5312; Váncza, Lóránd/0000-0003-0295-4732; Turiák, Lilla/0000-0002-2139-8156; Schaff, Zsuzsa/0000-0002-6429-8059; Kiss, András/0000-0002-7453-3163; Petővári, Gábor/0000-0002-1957-2864; Sebestyén, Anna/0000-0001-8814-4794; Dezső, Katalin/0000-0002-4856-0483; Tátrai, Péter/0000-0001-9726-1992; Baghy, Kornélia/0000-0002-5323-2775; Kovalszky, Ilona/0000-0002-0179-3378}
}

@article{MTMT:31881380,
	title = {Contribution of syndecans to the cellular entry of SARS-CoV-2},
	url = {https://m2.mtmt.hu/api/publication/31881380},
	author = {Hudák, Anett and Letoha, Annamária and Szilák, László and Letoha, Tamás},
	doi = {10.3390/ijms22105336},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {22},
	unique-id = {31881380},
	issn = {1661-6596},
	year = {2021},
	eissn = {1422-0067}
}

@article{MTMT:31615706,
	title = {Syndecan-1 Promotes Hepatocyte-Like Differentiation of Hepatoma Cells Targeting Ets-1 and AP-1},
	url = {https://m2.mtmt.hu/api/publication/31615706},
	author = {Hollósi, Péter and Váncza, Lóránd and Karászi, Katalin and Dobos, Katalin and Péterfia, Bálint and Tátrai, Enikő and Tátrai, Péter and Szarvas, Tibor and Paku, Sándor and Szilák, László and Kovalszky, Ilona},
	doi = {10.3390/biom10101356},
	journal-iso = {BIOMOLECULES},
	journal = {BIOMOLECULES},
	volume = {10},
	unique-id = {31615706},
	issn = {2218-273X},
	year = {2020},
	eissn = {2218-273X},
	orcid-numbers = {Hollósi, Péter/0000-0003-0458-8748; Váncza, Lóránd/0000-0003-0295-4732; Tátrai, Enikő/0000-0001-9778-2077; Tátrai, Péter/0000-0001-9726-1992; Szarvas, Tibor/0000-0002-6321-0799; Paku, Sándor/0000-0003-2664-7729; Kovalszky, Ilona/0000-0002-0179-3378}
}