scholarly journals Critical Protein–Protein Interactions Determine the Biological Activity of Elk-1, A Master Regulator of Stimulus-Induced Gene Transcription

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6125
Author(s):  
Gerald Thiel ◽  
Tobias M. Backes ◽  
Lisbeth A. Guethlein ◽  
Oliver G. Rössler
Keyword(s):  
Protein Kinase ◽  
Rna Polymerase Ii ◽  
Histone Deacetylase ◽  
Gene Transcription ◽  
Protein Interactions ◽  
Cellular Proliferation ◽  
Biological Function ◽  
Protein Protein Interactions ◽  
Inactive State ◽  
Serum Response

Elk-1 is a transcription factor that binds together with a dimer of the serum response factor (SRF) to the serum-response element (SRE), a genetic element that connects cellular stimulation with gene transcription. Elk-1 plays an important role in the regulation of cellular proliferation and apoptosis, thymocyte development, glucose homeostasis and brain function. The biological function of Elk-1 relies essentially on the interaction with other proteins. Elk-1 binds to SRF and generates a functional ternary complex that is required to activate SRE-mediated gene transcription. Elk-1 is kept in an inactive state under basal conditions via binding of a SUMO-histone deacetylase complex. Phosphorylation by extracellular signal-regulated protein kinase, c-Jun N-terminal protein kinase or p38 upregulates the transcriptional activity of Elk-1, mediated by binding to the mediator of RNA polymerase II transcription (Mediator) and the transcriptional coactivator p300. Strong and extended phosphorylation of Elk-1 attenuates Mediator and p300 recruitment and allows the binding of the mSin3A-histone deacetylase corepressor complex. The subsequent dephosphorylation of Elk-1, catalyzed by the protein phosphatase calcineurin, facilitates the re-SUMOylation of Elk-1, transforming Elk-1 back to a transcriptionally inactive state. Thus, numerous protein–protein interactions control the activation cycle of Elk-1 and are essential for its biological function.

scholarly journals The Functions of BET Proteins in Gene Transcription of Biology and Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Ka Lung Cheung ◽  
Claudia Kim ◽  
Ming-Ming Zhou
Keyword(s):  
Transcription Factors ◽  
Rna Polymerase Ii ◽  
Gene Transcription ◽  
Protein Interactions ◽  
Therapeutic Strategy ◽  
Regulation Of Gene Expression ◽  
Transcriptional Elongation ◽  
Protein Protein Interactions ◽  
Inflammatory Disorders ◽  
Damage Repair

The BET (bromodomain and extra-terminal domain) family proteins, consisting of BRD2, BRD3, BRD4, and testis-specific BRDT, are widely acknowledged as major transcriptional regulators in biology. They are characterized by two tandem bromodomains (BDs) that bind to lysine-acetylated histones and transcription factors, recruit transcription factors and coactivators to target gene sites, and activate RNA polymerase II machinery for transcriptional elongation. Pharmacological inhibition of BET proteins with BD inhibitors has been shown as a promising therapeutic strategy for the treatment of many human diseases including cancer and inflammatory disorders. The recent advances in bromodomain protein biology have further uncovered the complex and versatile functions of BET proteins in the regulation of gene expression in chromatin. In this review article, we highlight our current understanding of BET proteins’ functions in mediating protein–protein interactions required for chromatin-templated gene transcription and splicing, chromatin remodeling, DNA replication, and DNA damage repair. We further discuss context-dependent activator vs. repressor functions of individual BET proteins, isoforms, and bromodomains that may be harnessed for future development of BET bromodomain inhibitors as emerging epigenetic therapies for cancer and inflammatory disorders.

scholarly journals Targeted disruption of PKC from AKAP Signaling Complexes

2021 ◽  
Author(s):  
Ameya J. Limaye ◽  
George N. Bendzunas ◽  
Eileen Kennedy
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Targeted Disruption ◽  
Physiological Processes ◽  
Kinase C ◽  
P Protein

Protein Kinase C (PKC) is a member of the AGC subfamily of kinases and regulates a wide array of signaling pathways and physiological processes. Protein-protein interactions involving PKC and its...

scholarly journals Distinct Roles of PII-Like Signal Transmitter Proteins and amtB in Regulation of nif Gene Expression, Nitrogenase Activity, and Posttranslational Modification of NifH in Azoarcus sp. Strain BH72

2002 ◽  
Vol 184 (8) ◽  
pp. 2251-2259 ◽  
Author(s):  
Dietmar E. Martin ◽  
Barbara Reinhold-Hurek
Keyword(s):  
Gene Transcription ◽  
Protein Interactions ◽  
Double Mutant ◽  
Nitrogenase Activity ◽  
Covalent Modification ◽  
Ammonium Transporter ◽  
Protein Protein Interactions ◽  
Oxygen Control ◽  
Functional Inactivation ◽  
Signal Transduction Proteins

ABSTRACT PII-like signal transmitter proteins, found in Bacteria, Archaea, and plants, are known to mediate control of carbon and nitrogen assimilation. They indirectly regulate the activity of key metabolic enzymes and transcription factors by protein-protein interactions with signal transduction proteins. Many Proteobacteria harbor two paralogous PII-like proteins, GlnB and GlnK, whereas a novel third PII paralogue (GlnY) was recently identified in Azoarcus sp. strain BH72, a diazotrophic endophyte of grasses. In the present study, evidence was obtained that the PII-like proteins have distinct roles in mediating nitrogen and oxygen control of nif gene transcription and nitrogenase activity. Full repression of nif gene transcription in the presence of a combined nitrogen source or high oxygen concentrations was observed in wild-type and glnB and glnK knockout mutants, revealing that GlnB and GlnK can complement each other in mediating the repression. In contrast, in a glnBK double mutant strain in the presence of only GlnY, nif gene transcription was still detectable, albeit at a lower level, on nitrate or 20% oxygen. As another level of control, nitrogenase activity was regulated by at least three types of mechanisms in strain BH72: covalent modification of dinitrogenase reductase (NifH), probably by ADP-ribosylation, and two other, unknown means. Functional inactivation upon ammonium addition (switch-off) required the putative high-affinity ammonium transporter AmtB and GlnK, but not GlnB or GlnY. Functional inactivation in response to anaerobiosis did not depend on AmtB, GlnK, or GlnB. In contrast, covalent modification of NifH required both GlnB and GlnK and AmtB as response to ammonium addition, whereas it required either GlnB or GlnK and not AmtB when cells were shifted to anaerobiosis. In a glnBK double mutant expressing only GlnY, NifH modification was completely abolished, further revealing functional differences between the three PII paralogues.

scholarly journals Systematic identification of signal integration by protein kinase A

2015 ◽  
Vol 112 (14) ◽  
pp. 4501-4506 ◽  
Author(s):  
Marie Filteau ◽  
Guillaume Diss ◽  
Francisco Torres-Quiroz ◽  
Alexandre K. Dubé ◽  
Andrea Schraffl ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Protein Interactions ◽  
Carbon Sources ◽  
Biological Processes ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
Protein Complex Formation ◽  
Growth And Aging ◽  
Kinase A

Cellular processes and homeostasis control in eukaryotic cells is achieved by the action of regulatory proteins such as protein kinase A (PKA). Although the outbound signals from PKA directed to processes such as metabolism, growth, and aging have been well charted, what regulates this conserved regulator remains to be systematically identified to understand how it coordinates biological processes. Using a yeast PKA reporter assay, we identified genes that influence PKA activity by measuring protein–protein interactions between the regulatory and the two catalytic subunits of the PKA complex in 3,726 yeast genetic-deletion backgrounds grown on two carbon sources. Overall, nearly 500 genes were found to be connected directly or indirectly to PKA regulation, including 80 core regulators, denoting a wide diversity of signals regulating PKA, within and beyond the described upstream linear pathways. PKA regulators span multiple processes, including the antagonistic autophagy and methionine biosynthesis pathways. Our results converge toward mechanisms of PKA posttranslational regulation by lysine acetylation, which is conserved between yeast and humans and that, we show, regulates protein complex formation in mammals and carbohydrate storage and aging in yeast. Taken together, these results show that the extent of PKA input matches with its output, because this kinase receives information from upstream and downstream processes, and highlight how biological processes are interconnected and coordinated by PKA.

PKCε activation induces dichotomous cardiac phenotypes and modulates PKCε-RACK interactions and RACK expression

2001 ◽  
Vol 280 (3) ◽  
pp. H946-H955 ◽  
Author(s):  
Jason M. Pass ◽  
Yuting Zheng ◽  
William B. Wead ◽  
Jun Zhang ◽  
Richard C. X. Li ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Expression ◽  
Protein Interactions ◽  
Dominant Negative ◽  
The Other ◽  
Protein Protein Interactions ◽  
Kinase C ◽  
Transgenic Lines ◽  
Pkc Activation

Receptors for activated C kinase (RACKs) have been shown to facilitate activation of protein kinase C (PKC). However, it is unknown whether PKC activation modulates RACK protein expression and PKC-RACK interactions. This issue was studied in two PKCε transgenic lines exhibiting dichotomous cardiac phenotypes: one exhibits increased resistance to myocardial ischemia (cardioprotected phenotype) induced by a modest increase in PKCε activity (228 ± 23% of control), whereas the other exhibits cardiac hypertrophy and failure (hypertrophied phenotype) induced by a marked increase in PKCε activity (452 ± 28% of control). Our data demonstrate that activation of PKC modulates the expression of RACK isotypes and PKC-RACK interactions in a PKCε activity- and dosage-dependent fashion. We found that, in mice displaying the cardioprotected phenotype, activation of PKCε enhanced RACK2 expression (178 ± 13% of control) and particulate PKCε-RACK2 protein-protein interactions (178 ± 18% of control). In contrast, in mice displaying the hypertrophied phenotype, there was not only an increase in RACK2 expression (330 ± 33% of control) and particulate PKCε-RACK2 interactions (154 ± 14% of control) but also in RACK1 protein expression (174 ± 10% of control). Most notably, PKCε-RACK1 interactions were identified in this line. With the use of transgenic mice expressing a dominant negative PKCε, we found that the changes in RACK expression as well as the attending cardiac phenotypes were dependent on PKCε activity. Our observations demonstrate that RACK expression is dynamically regulated by PKCε and suggest that differential patterns of PKCε-RACK interactions may be important determinants of PKCε-dependent cardiac phenotypes.

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