Mapping Proximity Associations of Core Spindle Assembly Checkpoint Proteins

Garcia, Yenni A.; Velasquez, Erick F; Gao, Lucy; Gholkar, Ankur A.; Clutario, Kevin M.; Cheung, Keith; Williams-Hamilton, Taylor; Whitelegge, Julian P.; Torres, Jorge Z.

doi:10.1021/acs.jproteome.0c00941

Cited by 11 publications

(9 citation statements)

References 81 publications

(160 reference statements)

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“…The top four overrepresented BPs in the green module relate to a group of genes sharing important mitogenic activity. Genes such as MAD1L1 and CHAMP1 encode proteins that interact and regulate cell structure organization preceding mitosis ( 71 , 72 ). NR4A3 and NR1D2 encode transcriptional activators involved in proliferation, survival and differentiation of myeloid progenitor cells, and in adjusting myeloid progenitor cell metabolism to oxidative stress ( 73 , 74 ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional and Histochemical Signatures of Bone Marrow Mononuclear Cell-Mediated Resolution of Synovitis

et al. 2021

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Osteoarthritis (OA) may result from impaired ability of synovial macrophages to resolve joint inflammation. Increasing macrophage counts in inflamed joints through injection with bone marrow mononuclear cells (BMNC) induces lasting resolution of synovial inflammation. To uncover mechanisms by which BMNC may affect resolution, in this study, differential transcriptional signatures of BMNC in response to normal (SF) and inflamed synovial fluid (ISF) were analyzed. We demonstrate the temporal behavior of co-expressed gene networks associated with traits from related in vivo and in vitro studies. We also identified activated and inhibited signaling pathways and upstream regulators, further determining their protein expression in the synovium of inflamed joints treated with BMNC or DPBS controls. BMNC responded to ISF with an early pro-inflammatory response characterized by a short spike in the expression of a NF-ƙB- and mitogen-related gene network. This response was associated with sustained increased expression of two gene networks comprising known drivers of resolution (IL-10, IGF-1, PPARG, isoprenoid biosynthesis). These networks were common to SF and ISF, but more highly expressed in ISF. Most highly activated pathways in ISF included the mevalonate pathway and PPAR-γ signaling, with pro-resolving functional annotations that improve mitochondrial metabolism and deactivate NF-ƙB signaling. Lower expression of mevalonate kinase and phospho-PPARγ in synovium from inflamed joints treated with BMNC, and equivalent IL-1β staining between BMNC- and DPBS-treated joints, associates with accomplished resolution in BMNC-treated joints and emphasize the intricate balance of pro- and anti-inflammatory mechanisms required for resolution. Combined, our data suggest that BMNC-mediated resolution is characterized by constitutively expressed homeostatic mechanisms, whose expression are enhanced following inflammatory stimulus. These mechanisms translate into macrophage proliferation optimizing their capacity to counteract inflammatory damage and improving their general and mitochondrial metabolism to endure oxidative stress while driving tissue repair. Such effect is largely achieved through the synthesis of several lipids that mediate recovery of homeostasis. Our study reveals candidate mechanisms by which BMNC provide lasting improvement in patients with OA and suggests further investigation on the effects of PPAR-γ signaling enhancement for the treatment of arthritic conditions.

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Section: Discussionmentioning

confidence: 99%

Transcriptional and Histochemical Signatures of Bone Marrow Mononuclear Cell-Mediated Resolution of Synovitis

et al. 2021

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“…As examples, we recently used the analytical framework included in CANVS to study the PPI/A networks of DUSP7, which helped to define its regulation of ERK2 during mitosis ( Guo et al. , 2021 ), and to analyze the PPA networks of core spindle assembly checkpoint proteins ( Garcia et al. , 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…To test CANVS, we utilized a previously published mass spectrometry data set from BioID-based experiments of core spindle assembly checkpoint proteins ( Garcia et al. , 2021 ).…”

Section: Methodsmentioning

confidence: 99%

CANVS: an easy-to-use application for the analysis and visualization of mass spectrometry–based protein–protein interaction/association data

Velasquez

Garcia

Ramírez

et al. 2021

MBoC

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The elucidation of a protein's interaction/association network is important for defining its biological function. Mass spectrometry-based proteomic approaches have emerged as powerful tools for identifying protein-protein interactions (PPIs) and protein-protein associations (PPAs). However, interactome/association experiments are difficult to interpret considering the complexity and abundance of data that is generated. Although tools have been developed to quantitatively identify protein interactions/associations, there is still a pressing need for easy-to-use tools that allow users to contextualize their results. To address this, we developed CANVS, a computational pipeline that cleans, analyzes, and visualizes mass spectrometry-based interactome/association data. CANVS is wrapped as an interactive Shiny dashboard, allowing users to easily interface with the pipeline. With simple requirements, users can analyze complex experimental data and create PPI/A networks. The application integrates systems biology databases like BioGRID and CORUM to contextualize the results. Furthermore, CANVS features a Gene Ontology tool that allows users to identify relevant GO terms in their results and create visual networks with proteins associated with relevant GO terms. Overall, CANVS is an easy-to-use application that benefits all researchers, especially those who lack an established bioinformatic pipeline and are interested in studying interactome/association data.

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“…Several recently developed biotin ligases facilitate the measurement of PPIs including BioID2. BioID2 was initially developed as a smaller alternative to the BirA of E. coli BioID and has been utilized in experimental conditions to identify interacting proteins ( 9 , 22 , 23 , 24 ). Here, we report that truncation of the C terminus improved BioID2 labeling, whereas decreasing background biotinylation.…”

Section: Discussionmentioning

confidence: 99%