@article{MTMT:1915149,
	title = {Structurally Related Tpr Subunits Contribute Differently to The Function of The Anaphase-promoting Complex in Drosophila Melanogaster},
	url = {https://m2.mtmt.hu/api/publication/1915149},
	author = {Pál, Margit and Nagy, Olga Mária and Ménesi, Dalma and Udvardy, Andor and Deák, Péter},
	doi = {10.1242/jcs.004762},
	journal-iso = {J CELL SCI},
	journal = {JOURNAL OF CELL SCIENCE},
	volume = {120},
	unique-id = {1915149},
	issn = {0021-9533},
	abstract = {The anaphase-promoting complex/cyclosome or APC/C is a key regulator of chromosome segregation and mitotic exit in eukaryotes. It contains at least 11 subunits, most of which are evolutionarily conserved. The most abundant constituents of the vertebrate APC/C are the four structurally related tetratrico-peptide repeat (TPR) subunits, the functions of which are not yet precisely understood. Orthologues of three of the TPR subunits have been identified in Drosophila. We have shown previously that one of the TPR subunits of the Drosophila APC/C, Apc3 (also known as Cdc27 or Makos), is essential for development, and perturbation of its function results in mitotic cyclin accumulation and metaphase-like arrest. In this study we demonstrate that the Drosophila APC/C associates with a new TPR protein, a genuine orthologue of the vertebrate Apc7 subunit that is not found in yeasts. In addition to this, transgenic flies knocked down for three of the TPR genes Apc6 (Cdc16), Apc7 and Apc8 (Cdc23), by RNA interference were established to investigate their function. Whole-body expression of subunit-specific dsRNA efficiently silences these genes resulting in only residual mRNA concentrations. Apc6/Cdc16 and Apc8/Cdc23 silencing induces developmental delay and causes different pupal lethality. Cytological examination showed that these animals had an elevated level of apoptosis, high mitotic index and delayed or blocked mitosis in a prometaphase-metaphase-like state with overcondensed chromosomes. The arrested neuroblasts contained elevated levels of cyclin B but, surprisingly, cyclin A appeared to be degraded normally. Contrary to the situation for the Apc6/Cdc16 and Apc8/Cdc23 genes, the apparent loss of Apc7 function does not lead to the above abnormalities. Instead, the Apc7 knocked down animals and null mutants are viable and fertile, although they display mild chromosome segregation defects and anaphase delay. Nevertheless, the Apc7 subunit shows synergistic genetic interaction with Apc8/Cdc23 that, together with the phenotypic data, assumes a limited functional role for Apc7. Taken together, these data suggest that the structurally related TPR subunits contribute differently to the function of the anaphase-promoting complex.},
	year = {2007},
	eissn = {1477-9137},
	pages = {3238-3248},
	orcid-numbers = {Nagy, Olga Mária/0000-0003-1471-5165}
}

@article{MTMT:1912844,
	title = {Deletion of proteasomal subunit S5a/Rpn10/p54 causes lethality, multiple mitotic defects and overexpression of proteasomal genes in Drosophila melanogaster},
	url = {https://m2.mtmt.hu/api/publication/1912844},
	author = {Szlanka, Tamás and Haracska, Lajos and Kiss, István and Deák, Péter and Kurucz, Judit Éva and Andó, István and Virágh, Eszter Erika and Udvardy, Andor},
	doi = {10.1242/jcs.00332},
	journal-iso = {J CELL SCI},
	journal = {JOURNAL OF CELL SCIENCE},
	volume = {116},
	unique-id = {1912844},
	issn = {0021-9533},
	abstract = {The regulatory complex of the 26S proteasome is responsible for the selective recognition and binding of multiubiquitinated proteins. It was earlier shown that the subunit S5a/Rpn10/p54 of the regulatory complex is the only cellular protein capable of binding multiubiquitin chains in an in vitro overlay assay. The role of this subunit in substrate selection, however, is a subject of debate, following the observation that its deletion in Saccharomyces cerevisiae is not lethal and instead causes only a mild phenotype. To study the function of this subunit in higher eukaryotes, a mutant Drosophila strain was constructed by deleting the single copy gene encoding subunit S5a/Rpn10/p54. This deletion caused larval-pupal polyphasic lethality, multiple mitotic defects, the accumulation of higher multimers of ubiquitinated proteins and a huge accumulation of defective 26S proteasome particles. Deletion of the subunit S5a/Rpn10/p54 does not destabilise the regulatory complex and does not disturb the assembly of the regulatory complex and the catalytic core. The pupal lethality is a consequence of the depletion of the maternally provided 26S proteasome during the larval stages and a sudden increase in the proteasomal activity demands during the first few hours of pupal development. The huge accumulation of the fully assembled 26S proteasome in the deletion mutant and the lack of free subunits or partially assembled particles indicate that there is a highly coordinated accumulation of all the subunits of the 26S proteasome. This suggests that in higher eukaryotes, as with yeast, a feedback circuit coordinately regulates the expression of the proteasomal genes, and this adjusts the actual proteasome concentration in the cells according to the temporal and/or spatial proteolytic demands.},
	keywords = {Animals; Female; Female; Male; Male; PHENOTYPE; PHENOTYPE; YEAST; INSECT; MUTAGENESIS; review; Eukaryota; gene expression regulation; Saccharomyces cerevisiae; Saccharomyces cerevisiae; priority journal; controlled study; nonhuman; animal tissue; animal experiment; larva; larva; Animalia; MELANOGASTER; Protein Binding; in vitro study; enzyme activity; MOLECULAR RECOGNITION; Mitosis; Mitosis; Gene Expression Regulation, Developmental; Drosophila melanogaster; Drosophila melanogaster; Drosophila melanogaster; Gene Deletion; Gene Deletion; insecta; embryo; UBIQUITIN; Proteasome Endopeptidase Complex; proteasome; 26S PROTEASOME; concentration (parameters); Carrier Proteins; enzyme substrate; enzyme subunit; gene overexpression; lethality; eukaryote; protein degradation; feedback system; Peptide Hydrolases; Drosophila Proteins; protein assembly; Saccharomyces cerevisiae Proteins; Genes, Lethal; Pupa; Mitotic phenotype; Multiubiquitin binding subunit; Regulatory complex; S5a/Rpn10/p54 subunit},
	year = {2003},
	eissn = {1477-9137},
	pages = {1023-1033},
	orcid-numbers = {Andó, István/0000-0002-4648-9396}
}