The Yeast Saccharomyces cerevisiae as a Model for Understanding RAS Proteins and their Role in Human Tumorigenesis

Cazzanelli, Giulia; Pereira, Flávia; Alves, Sara; Francisco, Rita; Azevedo, Luı́sa; Carvalho, Patrícia Dias; Almeida, Ana F.; Côrte‐Real, Manuela; Oliveira, Maria José; Lucas, Cândida; Sousa, Maria João; Preto, Ana

doi:10.3390/cells7020014

Cited by 42 publications

(46 citation statements)

References 309 publications

(452 reference statements)

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“…This can be attributed to the fact that yeasts, being eukaryotes are quite similar to humans in terms of genes and other cellular pathways. It has been observed that the genes that regulate cellular processes in humans have equivalents that control cell division in yeasts as well which makes it very easy for pathogenic yeast species to alter the host cellular machinery (63). Therefore, this study has unravelled the potential mimicry candidates in fungal pathogens which was not well established till now.…”

Section: Motif Mimicrymentioning

confidence: 96%

ImitateDB: A Resource for Domain and Motif Mimicry in Host and Pathogen Proteins

Tayal

Bhatia

Mehrotra

et al. 2021

Preprint

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The host pathogen interactome can be visualized as a vast continuous network in which molecular mimicry of host proteins by pathogens constitutes a strategy to hijack the host pathways. Despite extensive work in this field, there is no dedicated resource for mimicked domains and motifs in host pathogen interactome. In this work, we collated all the data regarding the experimental host pathogen (HP) and host-host (HH) protein-protein interactions (PPIs). The domains and sequence linear motifs of the proteins were annotated using CD Search and ScanProsite. Host and pathogen proteins with a shared host interactor and similar domain/motif constitute a linear pair. A linear pair that exhibits global structural domain similarity (Domain linear pair; DLP) or local sequence motif similarity (Motif Linear Pair; MLP) has a high probability of being co-expressed and co-localized. 2,06,449 DLPs and 38,45,643 MLPs were identified in 50,812 experimental HP-PPIs and organized in a web- based resource, ImitateDB, accessible at http://imitatedb.sblab-nsit.net. ImitateDB provides user-friendly access to the mimicry data. It can be queried by protein UniProt ID, pathogen, domain, motif, or interaction detection method. The results are externally integrated using hyperlinked domain PSSM ID, motif ID and protein ID. Kinase, UL36, Smc and DEXDc were frequent DLP domains whereas Protein Kinase C, Casein Kinase 2, glycosylation and myristoylation sites were frequent MLP motifs. Novel DLP domains SANT, Tudor, PhoX and MLP motifs Microbodies C-terminal targeting signal, Ubiquitin-interacting motif and Lipocalin signature were proposed. ImitateDB constitutes a resource for researchers in the field of infectious diseases and microbiology.

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Section: Motif Mimicrymentioning

confidence: 96%

ImitateDB: A Resource for Domain and Motif Mimicry in Host and Pathogen Proteins

Tayal

Bhatia

Mehrotra

et al. 2021

Preprint

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“…On the other hand, the presence of nutrients in the cellular environment activates TOR complex (TORC), which prevents conjugation of Atg1p and Atg13p [241]. The nutrient availability has also been found to activate Ras signaling in both yeast and mammals [295][296][297]. In mammals, Ras signaling activates protein kinase B (Akt) in a cyclic AMP (cAMP)-dependent manner through adenylate cyclase activation [298].…”

Section: Conservation Of Autophagy Regulation In Yeast Modelsmentioning

confidence: 99%

Protein Homeostasis Networks and the Use of Yeast to Guide Interventions in Alzheimer’s Disease

Dhakal

Macreadie

2020

IJMS

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Alzheimer’s Disease (AD) is a progressive multifactorial age-related neurodegenerative disorder that causes the majority of deaths due to dementia in the elderly. Although various risk factors have been found to be associated with AD progression, the cause of the disease is still unresolved. The loss of proteostasis is one of the major causes of AD: it is evident by aggregation of misfolded proteins, lipid homeostasis disruption, accumulation of autophagic vesicles, and oxidative damage during the disease progression. Different models have been developed to study AD, one of which is a yeast model. Yeasts are simple unicellular eukaryotic cells that have provided great insights into human cell biology. Various yeast models, including unmodified and genetically modified yeasts, have been established for studying AD and have provided significant amount of information on AD pathology and potential interventions. The conservation of various human biological processes, including signal transduction, energy metabolism, protein homeostasis, stress responses, oxidative phosphorylation, vesicle trafficking, apoptosis, endocytosis, and ageing, renders yeast a fascinating, powerful model for AD. In addition, the easy manipulation of the yeast genome and availability of methods to evaluate yeast cells rapidly in high throughput technological platforms strengthen the rationale of using yeast as a model. This review focuses on the description of the proteostasis network in yeast and its comparison with the human proteostasis network. It further elaborates on the AD-associated proteostasis failure and applications of the yeast proteostasis network to understand AD pathology and its potential to guide interventions against AD.

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“…Great advances may beneficiate of simple model organisms enabling to dissect the complex network of genes and protein interactomes. To this end, yeast S. cerevisiae represents an awesome biological model for dissection of complex networks ( Cazzanelli et al, 2018 ) with a variety of molecular and genetic tools. The analysis of genetic interactions and the availability of yeast mutants in genes homolog to oncogenes and oncosuppressors may open to the identification of pathway-level interactions involved in oncogenic risk.…”

Section: Yeast Model and Saga Complexmentioning

confidence: 99%

Epigenetic Factors and Mitochondrial Biology in Yeast: A New Paradigm for the Study of Cancer Metabolism?

2018

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Bidirectional cross-talk between nuclear and mitochondrial DNA is fundamental for cell homeostasis. Epigenetic mechanisms regulate the inter-organelle communication between nucleus and mitochondria. Recent research highlights not only the retrograde activation of nuclear gene transcription in case of mitochondria dysfunction, but also the role of post-translational modifications of mitochondrial proteins in respiratory metabolism. Here we discuss some aspects and novel findings in Saccharomyces cerevisiae. In yeast, KAT-Gcn5 and DUB-Ubp8 have a role in respiration and are localized, as single proteins, into mitochondria. These findings, beside the canonical and widely known nuclear activity of SAGA complex in chromatin regulation, provide novel clues on promising aspects linking evolutionary conserved epigenetic factors to the re-programmed metabolism of cancer cells.

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The Yeast Saccharomyces cerevisiae as a Model for Understanding RAS Proteins and their Role in Human Tumorigenesis

Cited by 42 publications

References 309 publications

ImitateDB: A Resource for Domain and Motif Mimicry in Host and Pathogen Proteins

ImitateDB: A Resource for Domain and Motif Mimicry in Host and Pathogen Proteins

Protein Homeostasis Networks and the Use of Yeast to Guide Interventions in Alzheimer’s Disease

Epigenetic Factors and Mitochondrial Biology in Yeast: A New Paradigm for the Study of Cancer Metabolism?

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