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|Title:||SILAC-based phosphoproteomics reveals new PP2A-Cdc55-regulated processes in budding|
Bech-Serra, Joan J.
Torre Gómez, Carolina de la
Hernáez, María Luisa
Larsen, Martin R.
Queralt Badia, Ethel
|Publisher:||Oxford University Press|
|Abstract:||Background: Protein phosphatase 2A (PP2A) is a family of conserved serine/threonine phosphatases involved in several essential aspects of cell growth and proliferation. PP2A(Cdc55) phosphatase has been extensively related to cell cycle events in budding yeast; however, few PP2A(Cdc55) substrates have been identified. Here, we performed a quantitative mass spectrometry approach to reveal new substrates of PP2A(Cdc55) phosphatase and new PP2A-related processes in mitotic arrested cells. Results: We identified 62 statistically significant PP2A(Cdc55) substrates involved mainly in actin-cytoskeleton organization. In addition, we validated new PP2A(Cdc55) substrates such as Slk19 and Lte1, involved in early and late anaphase pathways, and Zeo1, a component of the cell wall integrity pathway. Finally, we constructed docking models of Cdc55 and its substrate Mob1. We found that the predominant interface on Cdc55 is mediated by a protruding loop consisting of residues 84-90, thus highlighting the relevance of these aminoacids for substrate interaction. Conclusions: We used phosphoproteomics of Cdc55-deficient cells to uncover new PP2A(Cdc55) substrates and functions in mitosis. As expected, several hyperphosphorylated proteins corresponded to Cdk1-dependent substrates, although other kinases' consensus motifs were also enriched in our dataset, suggesting that PP2A(Cdc55) counteracts and regulates other kinases distinct from Cdk1. Indeed, Pkc1 emerged as a novel node of PP2A(Cdc55) regulation, highlighting a major role of PP2A(Cdc55) in actin cytoskeleton and cytokinesis, gene ontology terms significantly enriched in the PP2A(Cdc55)-dependent phosphoproteome.|
|Note:||Reproducció del document publicat a: https://doi.org/10.1093/gigascience/giy047|
|It is part of:||Gigascience, 2018, vol. 7, num. 5|
|Appears in Collections:||Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))|
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