<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Identification of novel substrates of the Insoluble Protein Deposit (IPOD) in the yeast S. cerevisiae"^^ . "Cells have evolved elaborate protein quality control systems (PQS), which include molecular\r\nchaperones and proteolytic machineries. However, when the occurrence of misfolded\r\nproteins exceeds the PQS’s capacity, they accumulate and can form aggregates. More and\r\nmore evidence suggests that the accumulation of misfolded protein species into specific\r\nspatially separated deposition sites is a cytoprotective response of the cell. The yeast S.\r\ncerevisiae has at least three different such protein quality control sites: the JUxtaNuclear\r\nQuality control (JUNQ)/IntraNuclear Quality control site (INQ) and the Cyto-Q harbours\r\nunstructured, amorphously misfolded proteins, while the perivacuolar Insoluble PrOtein\r\nDeposit (IPOD) has been initially described as a deposition site for amyloid aggregates.\r\nHowever, more recently it has been suggested that the IPOD may also harbour other types of\r\nsubstrates, such as oxidatively damaged proteins and inactive/damaged proteasomes or\r\nsubunits thereof. Interestingly, many of these potential substrate classes can form high\r\nmolecular weight aggregates or represent large protein complexes, respectively. Because the\r\nIPOD lies directly adjacent to the phagophore assembly site at the vacuole, it was\r\nhypothesized that the perivacuolar IPOD may represent a sorting center for aggregates and\r\nlarger protein complexes destined for autophagic turnover. \r\n\r\nThis study focuses on the enrichment of IPODs visualized with the model substrate PrD-GFP\r\nunder different conditions, including oxidative stress, to characterize other IPOD substrates\r\nthrough an unbiased mass spectrometry approach. This strategy identified several proteins\r\nthat co-enriched with the IPOD, mainly after oxidative stress. Among these was Pyruvate\r\ndecarboxylase 1 (Pdc1), a protein susceptible to carbonylation which has been previously\r\nhypothesized to be present at the IPOD after oxidative insult. \r\n\r\nFor a Pdc1-mCh fusion protein, it was observed that the number of cells which formed Pdc1-mCh foci was increased after different forms of oxidative stress such as H2O2 or menadione\r\ntreatment. The majority of these stress-induced foci colocalized with PrD-GFP marked IPODs.\r\nOther proteins found enriched at the IPOD after oxidative stress include Enolase 2 (Eno2) and\r\nGlyceraldehyde-3-phosphate dehydrogenase isozyme 3 (Tdh3). Along these lines, by staining\r\nfor carbonylated proteins it was found that the overall levels of carbonylated proteins co-enriching with IPODs were much higher after application of oxidative stress. This supports\r\nthe hypothesis that aggregates of oxidatively damaged proteins are another substrate group for\r\nthe IPOD. \r\n\r\nFurthermore, it has been shown that aberrant stress granules transiently associate with the\r\naggresome on their way to autophagic degradation in mammalian cells. I hypothesized that\r\nthe IPOD may play a similar role to the aggresome in yeast in this regard and indeed, in a\r\ndCuz1 background that hinders proteasomal degradation of stress granules and makes them\r\nmore persistent, a proportion of aberrant arsenite-induced stress granules marked by Pab1mCh\r\ncolocalized with the IPOD after arsenite stress."^^ . "2023" . . . . . . . "Stephanie Tanja"^^ . "Zeuch"^^ . "Stephanie Tanja Zeuch"^^ . . . . . . "Identification of novel substrates of the Insoluble Protein Deposit (IPOD) in the yeast S. cerevisiae (PDF)"^^ . . . "PhD Dissertation_StephanieZeuch_13-01-2023.pdf"^^ . . . "Identification of novel substrates of the Insoluble Protein Deposit (IPOD) in the yeast S. cerevisiae (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Identification of novel substrates of the Insoluble Protein Deposit (IPOD) in the yeast S. cerevisiae (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Identification of novel substrates of the Insoluble Protein Deposit (IPOD) in the yeast S. cerevisiae (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Identification of novel substrates of the Insoluble Protein Deposit (IPOD) in the yeast S. cerevisiae (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Identification of novel substrates of the Insoluble Protein Deposit (IPOD) in the yeast S. cerevisiae (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #33035 \n\nIdentification of novel substrates of the Insoluble Protein Deposit (IPOD) in the yeast S. cerevisiae\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .