Signalling pathways and the regulation of SUMO modification

2007 ◽  
Vol 35 (6) ◽  
pp. 1414-1418 ◽  
Author(s):  
B. Guo ◽  
S.-H. Yang ◽  
J. Witty ◽  
A.D. Sharrocks
Keyword(s):  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Mitogen Activated Protein Kinase ◽  
Signalling Pathways ◽  
Protein Protein Interactions ◽  
E3 Ligases ◽  
Sumo Modification ◽  
Mitogen Activated Protein ◽  
The Impact ◽  
Protein Sumoylation

The modification of proteins by SUMO (small ubiquitin-related modifier) conjugation is becoming increasingly recognized as an important regulatory event. Protein SUMOylation can control a whole range of activities, including subcellular localization, protein–protein interactions and enzymatic activity. However, the SUMOylation process can itself be controlled. In the present review, the mechanisms through which protein SUMOylation is regulated are discussed, with particular emphasis on the impact of signalling pathways. A major point of regulation of the SUMO pathway is through targeting the E3 ligases, and a number of different ways to achieve this have been identified. More generally, the MAPK (mitogen-activated protein kinase) pathways represent one way through which SUMOylation of specific proteins is controlled, by using molecular mechanisms that at least in part also function by modifying the activity of SUMO E3 ligases. Further intricacies in signalling pathway interactions are hinted at through the growing number of examples of cross-talk between different post-translational modifications and SUMO modification.

scholarly journals Identification of key microRNAs in the carotid arteries of ApoE−/− mice exposed to disturbed flow

Hereditas ◽  
2019 ◽  
Vol 156 (1) ◽  
Author(s):  
Xinzhou Wang ◽  
Shuibo Gao ◽  
Liping Dai ◽  
Zhentao Wang ◽  
Hong Wu
Keyword(s):  
Blood Flow ◽  
Protein Interactions ◽  
Carotid Arteries ◽  
Target Genes ◽  
Pathological Process ◽  
Mitogen Activated Protein Kinase ◽  
Molecular Pathways ◽  
Protein Protein Interactions ◽  
Mitogen Activated Protein ◽  
Limma Package

Abstract Background Atherosclerosis (AS) is one of the main causes of cardiovascular disease. AS plaques often occur in blood vessels with oscillatory blood flow and their formation can be regulated by microRNAs (miRNAs). The aim of this study is to identify the key miRNAs and molecular pathways involved in this pathological process. Methods In this study, gene chip data obtained from the GEO database was analyzed using the LIMMA package to find differentially expressed miRNAs (DE miRNAs) in the carotid arteries of ApoE−/− mice exposed to different blood flow rates. Predicted targets of the DE miRNAs were identified using the TargetScan, miRDB, and DIANA databases respectively, and the potential target genes (PTGs) were found by analyzing the common results of three databases. The DAVID database was used to enrich the PTGs based on gene ontology (GO) and pathway (Kyoto Encyclopedia of Genes and Genomes, KEGG), and the STRING database was used to uncover any protein-protein interactions (PPI) of the PTGs. Results The networks of the DE miRNAs-PTGs, Pathway-PTGs-DE miRNAs, and PTGs PPI, were constructed using Cytoscape, and 11 up-regulated and 13 down-regulated DE miRNAs and 1479 PTGs were found. GO results showed that PTGs were significantly enriched in functions such as transcriptional regulation and DNA binding. KEGG results showed that PTGs were significantly enriched in inflammation-related mitogen-activated protein kinase (MAPK) and AS-related FOXO pathways. The PPI network revealed some key target genes in the PTGs. Conclusions The analysis of key miRNAs and molecular pathways that regulate the formation of AS plaques induced by oscillatory blood flow will provide new ideas for AS treatment.

scholarly journals Monitoring protein–protein interactions in mammalian cells by trans-SUMOylation

2011 ◽  
Vol 438 (3) ◽  
pp. 495-503 ◽  
Author(s):  
Ratnesh K. Srivastav ◽  
Susan Schwede ◽  
Malte Klaus ◽  
Jessica Schwermann ◽  
Matthias Gaestel ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Interactions ◽  
Mammalian Cells ◽  
Glutathione Transferase ◽  
Mitogen Activated Protein Kinase ◽  
Protein Protein Interactions ◽  
Sumoylation Site ◽  
Endogenous Expression ◽  
Mitogen Activated Protein

Protein–protein interactions are essential for almost all cellular processes, hence understanding these processes mainly depends on the identification and characterization of the relevant protein–protein interactions. In the present paper, we introduce the concept of TRS (trans-SUMOylation), a new method developed to identify and verify protein–protein interactions in mammalian cells in vivo. TRS utilizes Ubc9-fusion proteins that trans-SUMOylate co-expressed interacting proteins. Using TRS, we analysed interactions of 65 protein pairs co-expressed in HEK (human embryonic kidney)-293 cells. We identified seven new and confirmed 16 known protein interactions, which were determined via endogenous SUMOylation sites of the binding partners or by using SUMOylation-site tags respectively. Four of the new protein interactions were confirmed by GST (glutathione transferase) pull-down and the p38α–Edr2 interaction was verified by co-localization analysis. Functionally, this p38α–Edr2 interaction could possibly be involved in the recruitment of p38α to the polycomb chromatin-remodelling complex to phosphorylate Bmi1. We also used TRS to characterize protein-interaction domains of the protein kinase pairs p38α–MK2 [MK is MAPK (mitogen-activated protein kinase)-activated protein kinase] and ERK3 (extracellular-signal-regulated kinase 3)–MK5 and of the p38α–p53 complex. The ability of TRS to monitor protein interactions in mammalian cells in vivo at levels similar to endogenous expression makes it an excellent new tool that can help in defining the protein interactome of mammalian cells.

scholarly journals Stress- and mitogen-induced phosphorylation of the synapse-associated protein SAP90/PSD-95 by activation of SAPK3/p38gamma and ERK1/ERK2

2004 ◽  
Vol 380 (1) ◽  
pp. 19-30 ◽  
Author(s):  
Guadalupe SABIO ◽  
Suzana REUVER ◽  
Carmen FEIJOO ◽  
Masato HASEGAWA ◽  
Gareth M. THOMAS ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Interactions ◽  
Pdz Domain ◽  
Mitogen Activated Protein Kinase ◽  
Protein Protein Interactions ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
A Cell ◽  
Cellular Stresses ◽  
Sb 203580

SAPK3 (stress-activated protein kinase-3, also known as p38γ) is a member of the mitogen-activated protein kinase family; it phosphorylates substrates in response to cellular stress, and has been shown to bind through its C-terminal sequence to the PDZ domain of α1-syntrophin. In the present study, we show that SAP90 [(synapse-associated protein 90; also known as PSD-95 (postsynaptic density-95)] is a novel physiological substrate for both SAPK3/p38γ and the ERK (extracellular-signal-regulated protein kinase). SAPK3/p38γ binds preferentially to the third PDZ domain of SAP90 and phosphorylates residues Thr287 and Ser290in vitro, and Ser290 in cells in response to cellular stresses. Phosphorylation of SAP90 is dependent on the binding of SAPK3/p38γ to the PDZ domain of SAP90. It is not blocked by SB 203580, which inhibits SAPK2a/p38α and SAPK2b/p38β but not SAPK3/p38γ, or by the ERK pathway inhibitor PD 184352. However, phosphorylation is abolished when cells are treated with a cell-permeant Tat fusion peptide that disrupts the interaction of SAPK3/p38γ with SAP90. ERK2 also phosphorylates SAP90 at Thr287 and Ser290in vitro, but this does not require PDZ-dependent binding. SAP90 also becomes phosphorylated in response to mitogens, and this phosphorylation is prevented by pretreatment of the cells with PD 184352, but not with SB 203580. In neurons, SAP90 and SAPK3/p38γ co-localize and they are co-immunoprecipitated from brain synaptic junctional preparations. These results demonstrate that SAP90 is a novel binding partner for SAPK3/p38γ, a first physiological substrate described for SAPK3/p38γ and a novel substrate for ERK1/ERK2, and that phosphorylation of SAP90 may play a role in regulating protein–protein interactions at the synapse in response to adverse stress- or mitogenrelated stimuli.

scholarly journals Mutational Analysis of STE5 in the Yeast Saccharomyces cerevisiae: Application of a Differential Interaction Trap Assay for Examining Protein-Protein Interactions

Genetics ◽  
1997 ◽  
Vol 147 (2) ◽  
pp. 479-492 ◽  
Author(s):  
Carla Inouye ◽  
Namrita Dhillon ◽  
Tim Durfee ◽  
Patricia C Zambryski ◽  
Jeremy Thorner
Keyword(s):  
Protein Interactions ◽  
Mutational Analysis ◽  
Mapk Cascade ◽  
Mitogen Activated Protein Kinase ◽  
Missense Mutations ◽  
Protein Protein Interactions ◽  
Yeast Saccharomyces Cerevisiae ◽  
Mitogen Activated Protein

Ste5 is essential for the yeast mating pheromone response pathway and is thought to function as a scaffold that organizes the components of the mitogen-activated protein kinase (MAPK) cascade. A new method was developed to isolate missense mutations in Ste5 that differentially affect the ability of Ste5 to interact with either of two MAPK cascade constituents, the MEKK (Ste11) and the MEK (Ste7). Mutations that affect association with Ste7 or with Ste11 delineate discrete regions of Ste5 that are critical for each interaction. Co-immunoprecipitation analysis, examining the binding in vitro of Ste5 to Ste11, Ste7, Ste4 (G protein, β subunit), and Fus3 (MAPK), confirmed that each mutation specifically affects the interaction of Ste5 with only one protein. When expressed in a ste5Δ cell, mutant Ste5 proteins that are defective in their ability to interact with either Ste11 or Ste7 result in a markedly reduced mating proficiency. One mutation that clearly weakened (but did not eliminate) interaction of Ste5 with Ste7 permitted mating at wild-type efficiency, indicating that an efficacious signal is generated even when Ste5 associates with only a small fraction of (or only transiently with) Ste7. Ste5 mutants defective in association with Ste11 or Ste7 showed strong interallelic complementation when co-expressed, suggesting that the functional form of Ste5 in vivo is an oligomer.

scholarly journals Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions

2000 ◽  
Vol 351 (2) ◽  
pp. 289-305 ◽  
Author(s):  
Walter KOLCH
Keyword(s):  
Protein Interactions ◽  
Mitogen Activated Protein Kinase ◽  
Protein Protein Interactions ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Substrate Phosphorylation ◽  
Meaningful Relationships ◽  
Kinase Pathway

The Ras/Raf/MEK (mitogen-activated protein kinase/ERK kinase)/ERK (extracellular-signal-regulated kinase) pathway is at the heart of signalling networks that govern proliferation, differentiation and cell survival. Although the basic regulatory steps have been elucidated, many features of this pathway are only beginning to emerge. This review focuses on the role of protein–protein interactions in the regulation of this pathway, and how they contribute to co-ordinate activation steps, subcellular redistribution, substrate phosphorylation and cross-talk with other signalling pathways.

Tribbles in inflammation

2015 ◽  
Vol 43 (5) ◽  
pp. 1069-1074 ◽  
Author(s):  
Jessica Johnston ◽  
Shaghayegh Basatvat ◽  
Zabran Ilyas ◽  
Sheila Francis ◽  
Endre Kiss-Toth
Keyword(s):  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Current Knowledge ◽  
Innate Immune ◽  
Mitogen Activated Protein Kinase ◽  
Signalling Pathways ◽  
Disease Development ◽  
Mitogen Activated Protein ◽  
Phosphoinositide 3 Kinase ◽  
Inflammatory Signalling

Inflammation is part of the physiological innate immune response to invading pathogens and tissue injury. However, unresolved inflammation leads to human disease. The tribbles (TRIB) family of pseudokinase proteins has been shown to modulate key inflammatory signalling pathways, including the MAPK (mitogen-activated protein kinase) and PI3K (phosphoinositide 3-kinase) networks. This review summarizes our current knowledge on TRIBs in the context of inflammation, both at the level of molecular mechanisms and in disease development.

scholarly journals The Protein Interactome of Glycolysis in Escherichia coli

Proteomes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 16
Author(s):  
Shomeek Chowdhury ◽  
Stephen Hepper ◽  
Mudassir K. Lodi ◽  
Milton H. Saier ◽  
Peter Uetz
Keyword(s):  
Escherichia Coli ◽  
Protein Interactions ◽  
Allosteric Regulation ◽  
Glycolytic Enzymes ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Interacting Protein ◽  
E Coli ◽  
Protein Interactome ◽  
The Impact

Glycolysis is regulated by numerous mechanisms including allosteric regulation, post-translational modification or protein-protein interactions (PPI). While glycolytic enzymes have been found to interact with hundreds of proteins, the impact of only some of these PPIs on glycolysis is well understood. Here we investigate which of these interactions may affect glycolysis in E. coli and possibly across numerous other bacteria, based on the stoichiometry of interacting protein pairs (from proteomic studies) and their conservation across bacteria. We present a list of 339 protein-protein interactions involving glycolytic enzymes but predict that ~70% of glycolytic interactors are not present in adequate amounts to have a significant impact on glycolysis. Finally, we identify a conserved but uncharacterized subset of interactions that are likely to affect glycolysis and deserve further study.

Structure, Function, Involvement in Diseases and Targeting of 14-3-3 Proteins: An Update

2018 ◽  
Vol 25 (1) ◽  
pp. 5-21 ◽  
Author(s):  
Ylenia Cau ◽  
Daniela Valensin ◽  
Mattia Mori ◽  
Sara Draghi ◽  
Maurizio Botta
Keyword(s):  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
Specific Protein ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
Protein Partners ◽  
High Sequence Homology ◽  
Small Molecule Modulators

14-3-3 is a class of proteins able to interact with a multitude of targets by establishing protein-protein interactions (PPIs). They are usually found in all eukaryotes with a conserved secondary structure and high sequence homology among species. 14-3-3 proteins are involved in many physiological and pathological cellular processes either by triggering or interfering with the activity of specific protein partners. In the last years, the scientific community has collected many evidences on the role played by seven human 14-3-3 isoforms in cancer or neurodegenerative diseases. Indeed, these proteins regulate the molecular mechanisms associated to these diseases by interacting with (i) oncogenic and (ii) pro-apoptotic proteins and (iii) with proteins involved in Parkinson and Alzheimer diseases. The discovery of small molecule modulators of 14-3-3 PPIs could facilitate complete understanding of the physiological role of these proteins, and might offer valuable therapeutic approaches for these critical pathological states.

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