scholarly journals The role of 3′UTR-protein complexes in the regulation of protein multifunctionality and subcellular localization

2020 ◽  
Vol 48 (12) ◽  
pp. 6491-6502
Author(s):  
Diogo M Ribeiro ◽  
Alexis Prod’homme ◽  
Adrien Teixeira ◽  
Andreas Zanzoni ◽  
Christine Brun
Keyword(s):  
Protein Trafficking ◽  
Cellular Localization ◽  
Large Scale ◽  
Protein Complexes ◽  
Interaction Network ◽  
Multifunctional Proteins ◽  
Protein Protein Interaction ◽  
Moonlighting Proteins ◽  
Rna Interaction

Abstract Multifunctional proteins often perform their different functions when localized in different subcellular compartments. However, the mechanisms leading to their localization are largely unknown. Recently, 3′UTRs were found to regulate the cellular localization of newly synthesized proteins through the formation of 3′UTR-protein complexes. Here, we investigate the formation of 3′UTR-protein complexes involving multifunctional proteins by exploiting large-scale protein-protein and protein-RNA interaction networks. Focusing on 238 human ‘extreme multifunctional’ (EMF) proteins, we predicted 1411 3′UTR-protein complexes involving 54% of those proteins and evaluated their role in regulating protein cellular localization and multifunctionality. We find that EMF proteins lacking localization addressing signals, yet present at both the nucleus and cell surface, often form 3′UTR-protein complexes, and that the formation of these complexes could provide EMF proteins with the diversity of interaction partners necessary to their multifunctionality. Our findings are reinforced by archetypal moonlighting proteins predicted to form 3′UTR-protein complexes. Finally, the formation of 3′UTR-protein complexes that involves up to 17% of the proteins in the human protein-protein interaction network, may be a common and yet underestimated protein trafficking mechanism, particularly suited to regulate the localization of multifunctional proteins.

scholarly journals The role of 3’UTR-protein complexes in the regulation of protein multifunctionality and subcellular localization

2019 ◽  
Author(s):  
Diogo M. Ribeiro ◽  
Alexis Prod’homme ◽  
Adrien Teixeira ◽  
Andreas Zanzoni ◽  
Christine Brun
Keyword(s):  
Cellular Localization ◽  
Large Scale ◽  
Protein Complexes ◽  
Interaction Networks ◽  
Human Interactome ◽  
Multifunctional Proteins ◽  
Interaction Partners ◽  
Moonlighting Proteins ◽  
Rna Interaction

AbstractMultifunctional proteins often perform their different functions when localized in different subcellular compartments. However, the mechanisms leading to their localization are largely unknown. Recently, 3’UTRs were found to regulate the cellular localization of newly synthesized proteins through the co-translational formation of 3’UTR-protein complexes. Here, we investigate the formation of 3’UTR-protein complexes involving multifunctional proteins by exploiting large-scale protein-protein and protein-RNA interaction networks. Focusing on 238 human ‘extreme multifunctional’ (EMF) proteins, we predicted 1411 3’UTR-protein complexes involving 128 EMF proteins and evaluated their role in regulating protein cellular localization and multifunctionality. Notably, we find that EMF proteins lacking localization addressing signals, yet present at both the nucleus and cell surface, often form 3’UTR-protein complexes. In addition, they provide EMF proteins with the diversity of interaction partners necessary to their multifunctionality. Archetypal moonlighting proteins are also predicted to form 3’UTR-protein complexes thereby reinforcing our findings. Finally, our results indicate that the formation of 3’UTR-protein complex may be a common phenomenon in human cells, affecting up to 20% of the proteins in the human interactome.

scholarly journals A compendium of co-regulated protein complexes in breast cancer reveals collateral loss events

2017 ◽  
Author(s):  
Colm J. Ryan ◽  
Susan Kennedy ◽  
Ilirjana Bajrami ◽  
David Matallanas ◽  
Christopher J. Lord
Keyword(s):  
Breast Cancer ◽  
Large Scale ◽  
Transcriptional Control ◽  
Protein Complexes ◽  
Adherens Junction ◽  
Interaction Network ◽  
Cancer Subtypes ◽  
Protein Protein Interaction ◽  
Highly Correlated ◽  
E Cadherin

SummaryProtein complexes are responsible for the bulk of activities within the cell, but how their behavior and composition varies across tumors remains poorly understood. By combining proteomic profiles of breast tumors with a large-scale protein-protein interaction network, we have identified a set of 258 high-confidence protein complexes whose subunits have highly correlated protein abundance across tumor samples. We used this set to identify complexes that are reproducibly under- or over-expressed in specific breast cancer subtypes. We found that mutation or deletion of one subunit of a complex was often associated with a collateral reduction in protein expression of additional complex members. This collateral loss phenomenon was evident from proteomic, but not transcriptomic, profiles suggesting post-transcriptional control. Mutation of the tumor suppressor E-cadherin (CDH1)was associated with a collateral loss of members of the adherens junction complex, an effect we validated using an engineered model of E-cadherin loss.

scholarly journals Short loop functional commonality identified in leukaemia proteome highlights crucial protein sub-networks

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Sun Sook Chung ◽  
Joseph C F Ng ◽  
Anna Laddach ◽  
N Shaun B Thomas ◽  
Franca Fraternali
Keyword(s):  
Protein Interactions ◽  
Large Scale ◽  
Interaction Network ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Short Loop ◽  
New Strategy ◽  
Loop Network ◽  
Protein Protein Interaction Network

Abstract Direct drug targeting of mutated proteins in cancer is not always possible and efficacy can be nullified by compensating protein–protein interactions (PPIs). Here, we establish an in silico pipeline to identify specific PPI sub-networks containing mutated proteins as potential targets, which we apply to mutation data of four different leukaemias. Our method is based on extracting cyclic interactions of a small number of proteins topologically and functionally linked in the Protein–Protein Interaction Network (PPIN), which we call short loop network motifs (SLM). We uncover a new property of PPINs named ‘short loop commonality’ to measure indirect PPIs occurring via common SLM interactions. This detects ‘modules’ of PPI networks enriched with annotated biological functions of proteins containing mutation hotspots, exemplified by FLT3 and other receptor tyrosine kinase proteins. We further identify functional dependency or mutual exclusivity of short loop commonality pairs in large-scale cellular CRISPR–Cas9 knockout screening data. Our pipeline provides a new strategy for identifying new therapeutic targets for drug discovery.

scholarly journals Genome-wide identification of the GATA transcription factor family and their expression patterns under temperature and salt stress in Aspergillus oryzae

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chunmiao Jiang ◽  
Gongbo Lv ◽  
Jinxin Ge ◽  
Bin He ◽  
Zhe Zhang ◽  
...  
Keyword(s):  
Salt Stress ◽  
Expression Patterns ◽  
Interaction Network ◽  
Protein Protein Interaction ◽  
Genome Wide ◽  
Gata Transcription Factor ◽  
Starting Point ◽  
Evolutionary Features ◽  
First Time

AbstractGATA transcription factors (TFs) are involved in the regulation of growth processes and various environmental stresses. Although GATA TFs involved in abiotic stress in plants and some fungi have been analyzed, information regarding GATA TFs in Aspergillusoryzae is extremely poor. In this study, we identified and functionally characterized seven GATA proteins from A.oryzae 3.042 genome, including a novel AoSnf5 GATA TF with 20-residue between the Cys-X2-Cys motifs which was found in Aspergillus GATA TFs for the first time. Phylogenetic analysis indicated that these seven A. oryzae GATA TFs could be classified into six subgroups. Analysis of conserved motifs demonstrated that Aspergillus GATA TFs with similar motif compositions clustered in one subgroup, suggesting that they might possess similar genetic functions, further confirming the accuracy of the phylogenetic relationship. Furthermore, the expression patterns of seven A.oryzae GATA TFs under temperature and salt stresses indicated that A. oryzae GATA TFs were mainly responsive to high temperature and high salt stress. The protein–protein interaction network of A.oryzae GATA TFs revealed certain potentially interacting proteins. The comprehensive analysis of A. oryzae GATA TFs will be beneficial for understanding their biological function and evolutionary features and provide an important starting point to further understand the role of GATA TFs in the regulation of distinct environmental conditions in A.oryzae.

scholarly journals Synchronization of human retinal pigment epithelial-1 cells in mitosis

2020 ◽  
Vol 133 (18) ◽  
pp. jcs247940
Author(s):  
Stacey J. Scott ◽  
Kethan S. Suvarna ◽  
Pier Paolo D'Avino
Keyword(s):  
Cell Lines ◽  
Large Scale ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Interaction Network ◽  
Protein Protein Interaction ◽  
Pigment Epithelial ◽  
Adenocarcinoma Cells ◽  
Sequential Treatments

ABSTRACTHuman retinal pigment epithelial-1 (RPE-1) cells are increasingly being used as a model to study mitosis because they represent a non-transformed alternative to cancer cell lines, such as HeLa cervical adenocarcinoma cells. However, the lack of an efficient method to synchronize RPE-1 cells in mitosis precludes their application for large-scale biochemical and proteomics assays. Here, we report a protocol to synchronize RPE-1 cells based on sequential treatments with the Cdk4 and Cdk6 inhibitor PD 0332991 (palbociclib) and the microtubule-depolymerizing drug nocodazole. With this method, the vast majority (80–90%) of RPE-1 cells arrested at prometaphase and exited mitosis synchronously after release from nocodazole. Moreover, the cells fully recovered and re-entered the cell cycle after the palbociclib–nocodazole block. Finally, we show that this protocol could be successfully employed for the characterization of the protein–protein interaction network of the kinetochore protein Ndc80 by immunoprecipitation coupled with mass spectrometry. This synchronization method significantly expands the versatility and applicability of RPE-1 cells to the study of cell division and might be applied to other cell lines that do not respond to treatments with DNA synthesis inhibitors.

scholarly journals Synchronization of human retinal pigment ephitilial-1 (RPE-1) cells in mitosis

2020 ◽  
Author(s):  
Stacey J. Scott ◽  
Kethan Suvarna ◽  
Pier Paolo D’Avino
Keyword(s):  
Cell Lines ◽  
Large Scale ◽  
Retinal Pigment ◽  
Interaction Network ◽  
Protein Protein Interaction ◽  
Adenocarcinoma Cells ◽  
Sequential Treatments ◽  
Dna Synthesis Inhibitors ◽  
Protein Protein Interaction Network

ABSTRACTHuman retinal pigment ephitilial-1 (RPE-1) cells are increasingly being used as a model to study mitosis because they represent a non-transformed alternative to cancer cell lines, such as HeLa cervical adenocarcinoma cells. However, the lack of an efficient method to synchronize RPE-1 cells in mitosis precludes their application for large-scale biochemical and proteomics assays. Here we report a protocol to synchronize RPE-1 cells based on sequential treatments with the Cdk4/6 inhibitor PD 0332991 (palbociclib) and the microtubule depolymerizing drug nocodazole. With this method, the vast majority (80-90%) of RPE-1 cells arrested at prometaphase and exited mitosis synchronously after release from nocodazole. Furthermore, we show that this protocol could be successfully employed for the characterization of the protein-protein interaction network of the kinetochore protein Ndc80 by immunoprecipitation coupled with mass spectrometry. This synchronization method significantly expands the versatility and applicability of RPE-1 cells to the study of cell division and might be applied to other cell lines that do not respond to treatments with DNA synthesis inhibitors.

scholarly journals The diminishing role of hubs in dynamical processes on complex networks

2013 ◽  
Vol 10 (88) ◽  
pp. 20130568 ◽  
Author(s):  
Rick Quax ◽  
Andrea Apolloni ◽  
Peter M. A. Sloot
Keyword(s):  
Interaction Network ◽  
Macroscopic System ◽  
Protein Protein Interaction ◽  
Equilibrium Dynamics ◽  
Qualitative Evidence ◽  
Individual Unit ◽  
System Of Units ◽  
Protein Protein Interaction Network

It is notoriously difficult to predict the behaviour of a complex self-organizing system, where the interactions among dynamical units form a heterogeneous topology. Even if the dynamics of each microscopic unit is known, a real understanding of their contributions to the macroscopic system behaviour is still lacking. Here, we develop information-theoretical methods to distinguish the contribution of each individual unit to the collective out-of-equilibrium dynamics. We show that for a system of units connected by a network of interaction potentials with an arbitrary degree distribution, highly connected units have less impact on the system dynamics when compared with intermediately connected units. In an equilibrium setting, the hubs are often found to dictate the long-term behaviour. However, we find both analytically and experimentally that the instantaneous states of these units have a short-lasting effect on the state trajectory of the entire system. We present qualitative evidence of this phenomenon from empirical findings about a social network of product recommendations, a protein–protein interaction network and a neural network, suggesting that it might indeed be a widespread property in nature.

Dynamics of Protein-Protein Interaction Network in Plasmodium Falciparum

2009 ◽  
pp. 257-284
Author(s):  
Smita Mohanty ◽  
Shashi Bhushan Pandit ◽  
Narayanaswamy Srinivasan
Keyword(s):  
Plasmodium Falciparum ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
Cellular Localization ◽  
Interaction Network ◽  
Malarial Parasite ◽  
Strategic Integration ◽  
Protein Protein Interaction ◽  
Cellular Processes ◽  
Expression Of Genes

Integration of organism-wide protein interactome data with information on expression of genes, cellular localization of proteins and their functions has proved extremely useful in developing biologically intuitive interaction networks. This chapter highlights the dynamics in protein interaction network across different stages in the lifecycle of Plasmodium falciparum, a malarial parasite, and the implication of the network dynamics in different physiological processes. The main focus of the chapter is the integration of information on experimentally derived interactions of P.falciparum proteins with expression data and analysis of the implications of interactions in different cellular processes. Extensive analysis has been made to quantify the interaction dynamics across various stages, as well as correlating it with the dynamics of the cellular pathways involving the interacting proteins. The authors’ analysis demonstrates the power of strategic integration of genome-wide datasets in extracting information on dynamics of biological pathways and processes.

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