The BioGRID interaction database: 2019 update

Oughtred, Rose; Stark, Chris; Breitkreutz, Bobby-Joe; Rust, Jennifer; Boucher, Lorrie; Chang, Christie S.; Kolas, Nadine K.; O’Donnell, Lara; Leung, Genie; McAdam, Rochelle F.; Zhang, Frederick; Dolma, Sonam; Willems, Andrew; Coulombe-Huntington, Jasmin; Chatr‐aryamontri, Andrew; Dolinski, Kara; Tyers, Mike

doi:10.1093/nar/gky1079

Cited by 1,269 publications

(1,164 citation statements)

References 94 publications

(117 reference statements)

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“…Each organism appears to encode hundreds of Hero proteins with no apparent common motifs, and each Hero protein is likely to deal with many different client 1 6 proteins, thus providing a rich but complex source to mine. Indeed, Hero45, which was originally identified as an mRNA-binding protein (Heaton et al, 2001), has been found in the structure of the 80S ribosomes where it occupies the mRNA-binding channel (Habeck et al, 2013), but it is also known to be associated with hundreds of diverse proteins (Oughtred et al, 2019) with dynamic changes in its subcellular localizations in the cytoplasm, stress granules, nucleoli etc. (Lee et al, 2016(Lee et al, , 2014Yeom et al, 2015), highlighting the vast complexity of Hero proteins' actions.…”

Section: Discussionmentioning

confidence: 99%

A widespread family of heat-resistant obscure (Hero) proteins protect against protein instability and aggregation

Tsuboyama

Osaki

Suzuki-Matsuura

et al. 2019

Preprint

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Proteins are typically denatured and aggregated by heat. Exceptions to this principle include highly disordered and heat-resistant proteins found in extremophiles, which help these organisms tolerate extreme conditions such as drying, freezing, and high salinity.In contrast, the functions of heat-soluble proteins in non-extremophilic organisms including humans remain largely unexplored. Here we report that heat-resistant obscure (Hero) proteins, which remain soluble after boiling at 95ºC, are widespread in Drosophila and humans. Hero proteins are hydrophilic and highly charged, and function to stabilize various "client" proteins, protecting them from denaturation even under stress conditions such as heat shock, desiccation, and exposure to organic solvents. Hero proteins can also block several different types of pathological protein aggregations in cells, and in Drosophila strains that model neurodegenerative diseases. Moreover, some Hero proteins extend lifespan of Drosophila. Our study reveals that organisms naturally use Hero proteins as molecular shields to stabilize protein functions, highlighting their biotechnological and therapeutic potential.We are grateful to Qinghua Liu for providing the plasmids for Dicer-2 and R2D2 expression, Connie Cepko for pCAGEN vector, Drosophila

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Section: Discussionmentioning

confidence: 99%

A widespread family of heat-resistant obscure (Hero) proteins protect against protein instability and aggregation

Tsuboyama

Osaki

Suzuki-Matsuura

et al. 2019

Preprint

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“…Interaction network were generated using STRING's website (version 11.0) at high confidence (0.7) and network is clustered using a Markov Clustering algorithm “MCL inflation parameter = 3” (https://string-db.org/). BioGRID version 3.5.171 was used to extract known SCRIB and LANO interactors . The MS proteomics data, including search results, were deposited to the ProteomeXchange Consortium (http://www.proteomexchange.org) via the PRIDE partner repository with the dataset identifier PXD013636 and PXD013647.…”

Section: Methodsmentioning

confidence: 99%

The Tumor Suppressor SCRIB is a Negative Modulator of the Wnt/β‐Catenin Signaling Pathway

et al. 2019

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SCRIB is a scaffold protein containing leucine‐rich repeats (LRR) and PSD‐95/Dlg‐A/ZO‐1 domains (PDZ) that localizes at the basolateral membranes of polarized epithelial cells. Deregulation of its expression or localization leads to epithelial defects and tumorigenesis in part as a consequence of its repressive role on several signaling pathways including AKT, ERK, and HIPPO. In the present work, a proteomic approach is used to characterize the protein complexes associated to SCRIB and its paralogue LANO. Common and specific sets of proteins associated to SCRIB and LANO by MS are identified and an extensive landscape of their associated networks and the first comparative analysis of their respective interactomes are provided. Under proteasome inhibition, it is further found that SCRIB is associated to the β‐catenin destruction complex that is central in Wnt/β‐catenin signaling, a conserved pathway regulating embryonic development and cancer progression. It is shown that the SCRIB/β‐catenin interaction is potentiated upon Wnt3a stimulation and that SCRIB plays a repressing role on Wnt signaling. The data thus provide evidence for the importance of SCRIB in the regulation of the Wnt/β‐catenin pathway.

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“…Human protein-protein interactions (PPI) were downloaded from BioGRID version 3.3.123 (Oughtred et al, 2019) and non-physical interactions were removed, leaving 219,240 interactions. Additionally, an unweighted co-expression network of highly correlated genes, extracted from the GeneFriends co-expression map, was also used.…”

Section: Network Analysismentioning

confidence: 99%

Ageing Transcriptome Meta-Analysis Reveals Similarities Between Key Mammalian Tissues

Palmer

Fabris

Doherty

et al. 2019

Preprint

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Understanding the expression changes that come with age is an important step in understanding the ageing process as a whole. By combining such transcriptomic data with other sources of information, for instance protein-protein interaction (PPI) data, it is possible to make inferences about the functional changes that occur with age. To address this, we conducted a meta-analysis on 127 publicly available microarray and RNA-Seq datasets from mice, rats and humans, to identify genes that are commonly differentially expressed with age in mammals. We also conducted analyses on subsets of these datasets, to produce transcriptomic signatures for brain, heart and muscle tissues, all of which are important tissues in the pathophysiology of ageing. This approach identified the transcriptomic signatures of the ageing system, as well as brain, heart and muscle tissues. We then applied enrichment analysis and machine learning to functionally describe those signatures. This revealed a typical ageing signature including the overexpression of immune and stress response genes and the underexpression of metabolic and developmental genes. Further analysis of the ageing expression signatures revealed that genes differentially expressed with age tend to be broadly expressed across tissues, rather than be tissue-specific, and that the ageing expression signatures (particularly the overexpressed signatures) of the whole system, brain and muscle tend to include genes that are central in PPI networks. We also show that genes underexpressed in the brain are highly central in a co-expression map, suggesting that underexpression of these genes may play a part in cognitive ageing. In sum, we show numerous functional similarities between the ageing

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The BioGRID interaction database: 2019 update

Cited by 1,269 publications

References 94 publications

A widespread family of heat-resistant obscure (Hero) proteins protect against protein instability and aggregation

A widespread family of heat-resistant obscure (Hero) proteins protect against protein instability and aggregation

The Tumor Suppressor SCRIB is a Negative Modulator of the Wnt/β‐Catenin Signaling Pathway

Ageing Transcriptome Meta-Analysis Reveals Similarities Between Key Mammalian Tissues

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