@CONFERENCE{MTMT:34506866,
	title = {Usp5, Usp34, and Otu1 deubiquitylases mediate DNA repair in Drosophila melanogaster},
	url = {https://m2.mtmt.hu/api/publication/34506866},
	author = {Páhi, Zoltán Gábor and Kovács, Levente and Szűcs, Diána and Borsos, Barbara Nikolett and Deák, Péter and Pankotai, Tibor},
	booktitle = {Ubiquitin & Friends Symposium 2023},
	unique-id = {34506866},
	year = {2023},
	pages = {67-67},
	orcid-numbers = {Páhi, Zoltán Gábor/0000-0002-3428-553X; Kovács, Levente/0000-0002-3226-3740; Pankotai, Tibor/0000-0001-9810-5465}
}

@article{MTMT:34431874,
	title = {The ubiquitin thioesterase YOD1 ameliorates mutant Huntingtin induced pathology in Drosophila},
	url = {https://m2.mtmt.hu/api/publication/34431874},
	author = {Farkas, Anita and Zsindely, Nóra and Nagy, Gábor and Kovács, Levente and Deák, Péter and Bodai, László},
	doi = {10.1038/s41598-023-49241-8},
	journal-iso = {SCI REP},
	journal = {SCIENTIFIC REPORTS},
	volume = {13},
	unique-id = {34431874},
	issn = {2045-2322},
	abstract = {Huntington’s disease (HD) is a neurodegenerative disorder caused by a dominant gain-of-function mutation in the huntingtin gene, resulting in an elongated polyglutamine repeat in the mutant Huntingtin (mHtt) that mediates aberrant protein interactions. Previous studies implicated the ubiquitin–proteasome system in HD, suggesting that restoring cellular proteostasis might be a key element in suppressing pathology. We applied genetic interaction tests in a Drosophila model to ask whether modulating the levels of deubiquitinase enzymes affect HD pathology. By testing 32 deubiquitinase genes we found that overexpression of Yod1 ameliorated all analyzed phenotypes, including neurodegeneration, motor activity, viability, and longevity. Yod1 did not have a similar effect in amyloid beta overexpressing flies, suggesting that the observed effects might be specific to mHtt. Yod1 overexpression did not alter the number of mHtt aggregates but moderately increased the ratio of larger aggregates. Transcriptome analysis showed that Yod1 suppressed the transcriptional effects of mHtt and restored the expression of genes involved in neuronal plasticity, vesicular transport, antimicrobial defense, and protein synthesis, modifications, and clearance. Furthermore, Yod1 overexpression in HD flies leads to the upregulation of genes involved in transcriptional regulation and synaptic transmission, which might be part of a response mechanism to mHtt-induced stress.},
	year = {2023},
	eissn = {2045-2322},
	orcid-numbers = {Zsindely, Nóra/0000-0002-6189-3100; Nagy, Gábor/0000-0001-5464-1135; Kovács, Levente/0000-0002-3226-3740; Bodai, László/0000-0001-8411-626X}
}

@article{MTMT:33833753,
	title = {Targeting Drosophila Sas6 to mitochondria reveals its high affinity for Gorab},
	url = {https://m2.mtmt.hu/api/publication/33833753},
	author = {Kovács, Levente and Fatalska, Agnieszka and Glover, David M.},
	doi = {10.1242/bio.059545},
	journal-iso = {BIOL OPEN},
	journal = {BIOLOGY OPEN},
	volume = {11},
	unique-id = {33833753},
	issn = {2046-6390},
	abstract = {The ability to relocalize proteins to defined subcellular locations presents a powerful tool to examine protein-protein interactions that can overcome a tendency of non-targeted exogenous proteins to form inaccessible aggregates. Here, we show that a 24-amino-acid sequence from the Drosophila proapoptotic protein Hid's tail anchor (HTA) domain can target exogenous proteins to the mitochondria in Drosophila cells. We use this HTA tag to target the Drosophila centriole cartwheel protein Sas6 to the mitochondria, and show that both exogenous and endogenous Gorab can be co-recruited from the Golgi to the new mitochondrial site. This accords with our previous observation that monomeric Drosophila Gorab binds Sas6 to become centriole associated with a 50-fold greater affinity than dimeric Gorab binds Rab6 to become localized at the Golgi. Strikingly, Drosophila Sas6 can bind both Drosophila Gorab and its human GORAB ortholog, whereas human SAS6 is unable to bind either GORAB or Gorab. We discuss these findings in relation to the evolutionary conservation of Gorab and the divergence of Sas6, possibly reflecting known differences in persistence of the cartwheel in the centriole duplication cycle of fly and human cells.},
	year = {2022},
	eissn = {2046-6390},
	orcid-numbers = {Kovács, Levente/0000-0002-3226-3740; Fatalska, Agnieszka/0000-0002-1720-4742; Glover, David M./0000-0003-0956-0103}
}

@article{MTMT:32778093,
	title = {Usp5, Usp34, and Otu1 deubiquitylases mediate DNA repair in Drosophila melanogaster},
	url = {https://m2.mtmt.hu/api/publication/32778093},
	author = {Páhi, Zoltán Gábor and Kovács, Levente and Szűcs, Diána and Borsos, Barbara Nikolett and Deák, Péter and Pankotai, Tibor},
	doi = {10.1038/s41598-022-09703-x},
	journal-iso = {SCI REP},
	journal = {SCIENTIFIC REPORTS},
	volume = {12},
	unique-id = {32778093},
	issn = {2045-2322},
	year = {2022},
	eissn = {2045-2322},
	orcid-numbers = {Páhi, Zoltán Gábor/0000-0002-3428-553X; Kovács, Levente/0000-0002-3226-3740; Pankotai, Tibor/0000-0001-9810-5465}
}

@article{MTMT:32691300,
	title = {Loss of ubiquitinated protein autophagy is compensated by persistent cnc/NFE2L2/Nrf2 antioxidant responses},
	url = {https://m2.mtmt.hu/api/publication/32691300},
	author = {Bhattacharjee, Arindam and Harmatos-Ürmösi, Adél and Jipa, András and Kovács, Levente and Deák, Péter and Szabó, Áron and Juhász, Gábor},
	doi = {10.1080/15548627.2022.2037852},
	journal-iso = {AUTOPHAGY},
	journal = {AUTOPHAGY},
	volume = {18},
	unique-id = {32691300},
	issn = {1554-8627},
	year = {2022},
	eissn = {1554-8635},
	pages = {2385-2396},
	orcid-numbers = {Jipa, András/0000-0003-4880-7666; Kovács, Levente/0000-0002-3226-3740; Juhász, Gábor/0000-0001-8548-8874}
}

@{MTMT:32576298,
	title = {The role of E3 ubiquitin ligases in the regulation of crinophagy},
	url = {https://m2.mtmt.hu/api/publication/32576298},
	author = {Anna, Dósa and Csizmadia, Tamás and Maddali, Asha Kiran and Laczkó-Dobos, Hajnalka and Jipa, András and Kovács, Levente and Deák, Péter and Lőw, Péter and Juhász, Gábor},
	booktitle = {Hungarian Molecular Life Sciences 2021},
	unique-id = {32576298},
	abstract = {Crinophagy is a special form of autophagy, in which damaged or no longer needed secretory granules
		directly fuse with lysosomes, independently from autophagosome formation. Our colleagues have
		previously identified the molecular components of the membrane fusion apparatus (SNARE proteins,
		small GTPases and the tethering complex), using Drosophila melanogaster as a model organism, in
		which crinophagy is part of the normal developmental program of the larval salivary gland. Despite
		these findings, our knowledge is still little about the complete mechanism, as the upstream regulation
		of the process remains mainly unclear. The well-known function of ubiquitin is the targeting of
		cytoplasmic proteins into the proteasome for degradation, maintaining normal protein turnover.
		However, it has been observed that ubiquitin plays important roles in many other cellular processes,
		such as signal transduction or proteasome-independent degradation. It has been previously shown
		that in yeast, an E3 ubiquitin ligase activity is needed for the fast degradation of the gluconeogenic
		enzymes through the Vacuolar Import and Degradation (Vid) pathway, which is mechanistically similar
		to crinophagy. According to these data, ubiquitin could potentially have a role in the regulation of
		crinophagy, too, so our group decided to investigate this possibility.
		In our work, using fluorescent and immunocytochemical labeling methods, we have found ubiquitin
		on the surface of (glue) secretory granules, when crinophagy is activated. Moreover, through a small-
		scale genetic screen that involved the genes of E3 ubiquitin ligases, we identified one E3 enzyme which
		is required for the initiation of developmentally programmed crinophagy. Importantly, the
		overexpression of this enzyme causes early induction of secretory granule-lysosome fusion. We
		observed these phenotypes using both fluorescent and electron microscopy techniques.
		According to these results, E3 ubiquitin ligase activity is likely needed for successful crinophagy, thus
		we predict that at least one ubiquitination event occurs in the process of crinophagy},
	year = {2021},
	pages = {1},
	orcid-numbers = {Csizmadia, Tamás/0000-0002-2098-9165; Jipa, András/0000-0003-4880-7666; Kovács, Levente/0000-0002-3226-3740; Lőw, Péter/0000-0003-2450-7087; Juhász, Gábor/0000-0001-8548-8874}
}

@{MTMT:32576272,
	title = {The role of ubiquitin in the secretory granule degradation in Drosophila},
	url = {https://m2.mtmt.hu/api/publication/32576272},
	author = {Csizmadia, Tamás and Dósa, Anna and Maddali, Asha Kiran and Laczkó-Dobos, Hajnalka and Jipa, András and Kovács, Levente and Deák, Péter and Lőw, Péter and Juhász, Gábor},
	booktitle = {Hungarian Molecular Life Sciences 2021},
	unique-id = {32576272},
	abstract = {In the late larval period of Drosophila salivary gland, part of the glue containing secretory granules
		evade exocytosis and are degraded via crinophagy. During this process the obsolete secretory vesicles
		directly fuse with late endosomes or lysosomes for the fast degradation and recycling of the secretory
		cargo. The mechanism of secretory granule assortment for degradation is unknown since the
		discovery of crinophagy. Here we show that, the obsolete secretory granules are designated for
		degradation by ubiquitin (Figure 1) before their fusion with late endosomes/lysosomes. Moreover, we
		have identified the molecular components (E3 and deubiquitinating enzymes), which are involved in
		the ubiquitination of secretory (glue) granule membrane proteins. Importantly, the activity of these
		components is required for the normal crinophagic degradation of unnecessary secretory vesicles.
		Our work establishes the molecular background, which directs obsolete secretory granules for
		developmentally programmed crinophagy in Drosophila and paves the way for analyzing and
		understanding the regulation of this process in Metazoan},
	year = {2021},
	pages = {0},
	orcid-numbers = {Csizmadia, Tamás/0000-0002-2098-9165; Jipa, András/0000-0003-4880-7666; Kovács, Levente/0000-0002-3226-3740; Lőw, Péter/0000-0003-2450-7087; Juhász, Gábor/0000-0001-8548-8874}
}

@article{MTMT:32367729,
	title = {The dimeric Golgi protein Gorab binds to Sas6 as a monomer to mediate centriole duplication},
	url = {https://m2.mtmt.hu/api/publication/32367729},
	author = {Fatalska, Agnieszka and Stepinac, Emma and Richter, Magdalena and Kovács, Levente and Pietras, Zbigniew and Puchinger, Martin and Dong, Gang and Dadlez, Michal and Glover, David M.},
	doi = {10.7554/eLife.57241},
	journal-iso = {ELIFE},
	journal = {ELIFE},
	volume = {10},
	unique-id = {32367729},
	issn = {2050-084X},
	abstract = {The duplication and ninefold symmetry of the Drosophila centriole requires that the cartwheel molecule, Sas6, physically associates with Gorab, a trans-Golgi component. How Gorab achieves these disparate associations is unclear. Here, we use hydrogen-deuterium exchange mass spectrometry to define Gorab's interacting surfaces that mediate its subcellular localization. We identify a core stabilization sequence within Gorab's C-terminal coiled-coil domain that enables homodimerization, binding to Rab6, and thereby trans-Golgi localization. By contrast, part of the Gorab monomer's coiled-coil domain undergoes an antiparallel interaction with a segment of the parallel coiled-coil dimer of Sas6. This stable heterotrimeric complex can be visualized by electron microscopy. Mutation of a single leucine residue in Sas6's Gorab-binding domain generates a Sas6 variant with a sixteenfold reduced binding affinity for Gorab that cannot support centriole duplication. Thus, Gorab dimers at the Golgi exist in equilibrium with Sas6-associated monomers at the centriole to balance Gorab's dual role.},
	year = {2021},
	eissn = {2050-084X},
	orcid-numbers = {Fatalska, Agnieszka/0000-0002-1720-4742; Kovács, Levente/0000-0002-3226-3740; Dong, Gang/0000-0001-9745-8103}
}

@article{MTMT:31383527,
	title = {Tissue specific requirement of Drosophila Rcd4 for centriole duplication and ciliogenesis},
	url = {https://m2.mtmt.hu/api/publication/31383527},
	author = {Panda, P. and Kovács, Levente and Dzhindzhev, N. and Fatalska, A. and Persico, V. and Geymonat, M. and Riparbelli, M.G. and Callaini, G. and Glover, D.M.},
	doi = {10.1083/jcb.201912154},
	journal-iso = {J CELL BIOL},
	journal = {JOURNAL OF CELL BIOLOGY},
	volume = {219},
	unique-id = {31383527},
	issn = {0021-9525},
	abstract = {Rcd4 is a poorly characterized Drosophila centriole component whose mammalian counterpart, PPP1R35, is suggested to function in centriole elongation and conversion to centrosomes. Here, we show that rcd4 mutants exhibit fewer centrioles, aberrant mitoses, and reduced basal bodies in sensory organs. Rcd4 interacts with the C-terminal part of Ana3, which loads onto the procentriole during interphase, ahead of Rcd4 and before mitosis. Accordingly, depletion of Ana3 prevents Rcd4 recruitment but not vice versa. We find that neither Ana3 nor Rcd4 participates directly in the mitotic conversion of centrioles to centrosomes, but both are required to load Ana1, which is essential for such conversion. Whereas ana3 mutants are male sterile, reflecting a requirement for Ana3 for centriole development in the male germ line, rcd4 mutants are fertile and have male germ line centrioles of normal length. Thus, Rcd4 is essential in somatic cells but is not absolutely required in spermatogenesis, indicating tissue-specific roles in centriole and basal body formation. © 2020 Panda et al.},
	keywords = {Adult; Male; ARTICLE; DROSOPHILA; nonhuman; Mitosis; Spermatogenesis; human cell; germ line; Interphase; somatic cell; centriole; kinetosome; Sense organ},
	year = {2020},
	eissn = {1540-8140},
	orcid-numbers = {Kovács, Levente/0000-0002-3226-3740}
}

@article{MTMT:31158977,
	title = {Usp14 is required for spermatogenesis and ubiquitin stress responses in Drosophila melanogaster.},
	url = {https://m2.mtmt.hu/api/publication/31158977},
	author = {Kovács, Levente and Nagy, Ágota and Pál, Margit and Deák, Péter},
	doi = {10.1242/jcs.237511},
	journal-iso = {J CELL SCI},
	journal = {JOURNAL OF CELL SCIENCE},
	volume = {133},
	unique-id = {31158977},
	issn = {0021-9533},
	abstract = {Deubiquitylating (DUB) enzymes free covalently linked ubiquitin moieties from ubiquitin-ubiquitin and ubiquitin-protein conjugates, and thereby maintain the equilibrium between free and conjugated ubiquitin moieties and regulate ubiquitin-mediated cellular processes. Here, we performed genetic analyses of mutant phenotypes in Drosophila melanogaster and demonstrate that loss of Usp14 function results in male sterility, with defects in spermatid individualization and reduced testicular free monoubiquitin levels. These phenotypes were rescued by germline-specific overexpression of wild-type Usp14. Synergistic genetic interactions with Ubi-p63E and cycloheximide sensitivity suggest that ubiquitin shortage is a primary cause of male sterility. In addition, Usp14 is predominantly expressed in testes in Drosophila, indicating a higher demand for this DUB in testes that is also reflected by testis-specific loss-of-function Usp14 phenotypes. Collectively, these results suggest a major role of Usp14 in maintaining normal steady state free monoubiquitin levels during the later stages of Drosophila spermatogenesis.This article has an associated First Person interview with the first author of the paper.},
	keywords = {deubiquitination; USP14; Deubiquitylaton; Drosophila spermatogenesis; Ubiquitin equilibrium},
	year = {2020},
	eissn = {1477-9137},
	orcid-numbers = {Kovács, Levente/0000-0002-3226-3740}
}