Simulation Methods in Uncovering New Regulatory Mechanisms in Signaling Pathways

2009 ◽  
pp. 400-408
Author(s):  
Jarosław Smieja
Keyword(s):  
Signaling Pathways ◽  
Regulatory Mechanisms ◽  
Simulation Methods

scholarly journals The Multifaceted Roles of USP15 in Signal Transduction

2021 ◽  
Vol 22 (9) ◽  
pp. 4728
Author(s):  
Tanuza Das ◽  
Eun Joo Song ◽  
Eunice EunKyeong Kim
Keyword(s):  
Signal Transduction ◽  
Signaling Pathways ◽  
Cellular Networks ◽  
Clinical Applications ◽  
Regulatory Mechanisms ◽  
Signaling Networks ◽  
Post Translational Modification ◽  
Comprehensive Overview ◽  
E3 Ligases ◽  
Disease Markers

Ubiquitination and deubiquitination are protein post-translational modification processes that have been recognized as crucial mediators of many complex cellular networks, including maintaining ubiquitin homeostasis, controlling protein stability, and regulating several signaling pathways. Therefore, some of the enzymes involved in ubiquitination and deubiquitination, particularly E3 ligases and deubiquitinases, have attracted attention for drug discovery. Here, we review recent findings on USP15, one of the deubiquitinases, which regulates diverse signaling pathways by deubiquitinating vital target proteins. Even though several basic previous studies have uncovered the versatile roles of USP15 in different signaling networks, those have not yet been systematically and specifically reviewed, which can provide important information about possible disease markers and clinical applications. This review will provide a comprehensive overview of our current understanding of the regulatory mechanisms of USP15 on different signaling pathways for which dynamic reverse ubiquitination is a key regulator.

scholarly journals Activation of signaling pathways and regulatory mechanisms of mRNA translation following myocardial ischemia-reperfusion

2006 ◽  
Vol 101 (2) ◽  
pp. 576-582 ◽  
Author(s):  
Stephen J. Crozier ◽  
Xueqian Zhang ◽  
Jufang Wang ◽  
Joseph Cheung ◽  
Scot R. Kimball ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Myocardial Ischemia ◽  
Protein Expression ◽  
Signaling Pathways ◽  
Mrna Translation ◽  
Mitogen Activated Protein Kinase ◽  
Regulatory Mechanisms ◽  
Ischemia And Reperfusion ◽  
Myocardial Ischemia And Reperfusion ◽  
Mitogen Activated Protein

Protein expression in the heart is altered following periods of myocardial ischemia. The changes in protein expression are associated with increased cell size that can be maladaptive. There is little information regarding the regulation of protein expression through the process of mRNA translation during ischemia and reperfusion in the heart. Therefore, the purpose of this study was to identify changes in signaling pathways and downstream regulatory mechanisms of mRNA translation in an in vivo model of myocardial ischemia and reperfusion. Hearts were collected from rats whose left main coronary arteries had either been occluded for 25 min or reversibly occluded for 25 min and subsequently reperfused for 15 min. Following reperfusion, both the phosphoinositide 3-kinase and mitogen-activated protein kinase pathways were activated, as evidenced by increased phosphorylation of Akt (PKB), extracellular signal-regulated kinase 1/2, and p38 mitogen-activated protein kinase. Activation of Akt stimulated signaling through the protein kinase mammalian target of rapamycin, as evidenced by increased phosphorylation of two of its effectors, the ribosomal protein S6 kinase and the eukaryotic initiation factor eIF4E binding protein 1. Ischemia and reperfusion also resulted in increased phosphorylation of eIF2 and eIF2B. These changes in protein phosphorylation suggest that control of mRNA translation following ischemia and reperfusion is modulated through a number of signaling pathways and regulatory mechanisms.

scholarly journals Intricate Regulatory Mechanisms of the Anaphase-Promoting Complex/Cyclosome and Its Role in Chromatin Regulation

2021 ◽  
Vol 9 ◽  
Author(s):  
Tatyana Bodrug ◽  
Kaeli A. Welsh ◽  
Megan Hinkle ◽  
Michael J. Emanuele ◽  
Nicholas G. Brown
Keyword(s):  
Cell Cycle ◽  
Signaling Pathways ◽  
Biological Process ◽  
Conformational Dynamics ◽  
Intimate Relationship ◽  
Regulatory Mechanisms ◽  
Cell Cycle Regulators ◽  
Chromatin Regulation ◽  
Anaphase Promoting Complex

The ubiquitin (Ub)-proteasome system is vital to nearly every biological process in eukaryotes. Specifically, the conjugation of Ub to target proteins by Ub ligases, such as the Anaphase-Promoting Complex/Cyclosome (APC/C), is paramount for cell cycle transitions as it leads to the irreversible destruction of cell cycle regulators by the proteasome. Through this activity, the RING Ub ligase APC/C governs mitosis, G1, and numerous aspects of neurobiology. Pioneering cryo-EM, biochemical reconstitution, and cell-based studies have illuminated many aspects of the conformational dynamics of this large, multi-subunit complex and the sophisticated regulation of APC/C function. More recent studies have revealed new mechanisms that selectively dictate APC/C activity and explore additional pathways that are controlled by APC/C-mediated ubiquitination, including an intimate relationship with chromatin regulation. These tasks go beyond the traditional cell cycle role historically ascribed to the APC/C. Here, we review these novel findings, examine the mechanistic implications of APC/C regulation, and discuss the role of the APC/C in previously unappreciated signaling pathways.

scholarly journals Emerging crosstalk between two signaling pathways coordinates K+ and Na+ homeostasis in the halophyte Hordeum brevisubulatum

2020 ◽  
Vol 71 (14) ◽  
pp. 4345-4358
Author(s):  
Haiwen Zhang ◽  
Hao Feng ◽  
Junwen Zhang ◽  
Rongchao Ge ◽  
Liyuan Zhang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Regulatory Mechanisms ◽  
K Channel ◽  
Interacting Proteins ◽  
The Novel ◽  
Voltage Gated ◽  
Primary Core ◽  
High Salt Stress ◽  
Hordeum Brevisubulatum

Abstract K+/Na+ homeostasis is the primary core response for plant to tolerate salinity. Halophytes have evolved novel regulatory mechanisms to maintain a suitable K+/Na+ ratio during long-term adaptation. The wild halophyte Hordeum brevisubulatum can adopt efficient strategies to achieve synergistic levels of K+ and Na+ under high salt stress. However, little is known about its molecular mechanism. Our previous study indicated that HbCIPK2 contributed to prevention of Na+ accumulation and K+ reduction. Here, we further identified the HbCIPK2-interacting proteins including upstream Ca2+ sensors, HbCBL1, HbCBL4, and HbCBL10, and downstream phosphorylated targets, the voltage-gated K+ channel HbVGKC1 and SOS1-like transporter HbSOS1L. HbCBL1 combined with HbCIPK2 could activate HbVGKC1 to absorb K+, while the HbCBL4/10–HbCIPK2 complex modulated HbSOS1L to exclude Na+. This discovery suggested that crosstalk between the sodium response and the potassium uptake signaling pathways indeed exists for HbCIPK2 as the signal hub, and paved the way for understanding the novel mechanism of K+/Na+ homeostasis which has evolved in the halophytic grass.

scholarly journals Polyamines and related signaling pathways in cancer

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jiajing Li ◽  
Yan Meng ◽  
Xiaolin Wu ◽  
Yuxin Sun
Keyword(s):  
Systematic Review ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Treatment Strategies ◽  
Cancer Chemoprevention ◽  
Regulatory Mechanisms ◽  
Polyamine Metabolism ◽  
Amino Groups ◽  
Polyamine Synthesis ◽  
Aliphatic Compounds

Abstract Polyamines are aliphatic compounds with more than two amino groups that play various important roles in human cells. In cancer, polyamine metabolism dysfunction often occurs, and regulatory mechanisms of polyamine. This review summarizes the existing research on the metabolism and transport of polyamines to study the association of oncogenes and related signaling pathways with polyamines in tumor cells. Drugs that regulate enzymes have been developed for cancer treatment, and in the future, more attention should be paid to treatment strategies that simultaneously modulate polyamine metabolism and carcinogenic signaling pathways. In addition, the polyamine pathway is a potential target for cancer chemoprevention. As an irreversible suicide inhibitor of the ornithine decarboxylase (a vital enzyme of polyamine synthesis), Difluoro-methylornithine had been shown to have the chemoprevention effect on cancer. Therefore, we summarized and analyzed the chemoprophylaxis effect of the difluoromethylornithine in this systematic review.

The Complex Genetic Basis and Multilayered Regulatory Control of Yeast Pseudohyphal Growth

2021 ◽  
Vol 55 (1) ◽  
Author(s):  
Anuj Kumar
Keyword(s):  
Cell Growth ◽  
Signaling Pathways ◽  
Single Cells ◽  
Regulatory Control ◽  
Yeast Cells ◽  
Regulatory Mechanisms ◽  
Annual Review ◽  
Publication Date ◽  
Yeast Saccharomyces Cerevisiae ◽  
Pseudohyphal Growth

Eukaryotic cells are exquisitely responsive to external and internal cues, achieving precise control of seemingly diverse growth processes through a complex interplay of regulatory mechanisms. The budding yeast Saccharomyces cerevisiae provides a fascinating model of cell growth in its stress-responsive transition from planktonic single cells to a filamentous pseudohyphal growth form. During pseudohyphal growth, yeast cells undergo changes in morphology, polarity, and adhesion to form extended and invasive multicellular filaments. This pseudohyphal transition has been studied extensively as a model of conserved signaling pathways regulating cell growth and for its relevance in understanding the pathogenicity of the related opportunistic fungus Candida albicans, wherein filamentous growth is required for virulence. This review highlights the broad gene set enabling yeast pseudohyphal growth, signaling pathways that regulate this process, the role and regulation of proteins conferring cell adhesion, and interesting regulatory mechanisms enabling the pseudohyphal transition. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals The molecular tug of war between immunity and fertility: Emergence of conserved signaling pathways and regulatory mechanisms

BioEssays ◽  
2020 ◽  
Vol 42 (12) ◽  
pp. 2000103 ◽  
Author(s):  
Nikki Naim ◽  
Francis R.G. Amrit ◽  
T. Brooke McClendon ◽  
Judith L. Yanowitz ◽  
Arjumand Ghazi
Keyword(s):  
Signaling Pathways ◽  
Regulatory Mechanisms

scholarly journals Protein Kinase A and Sch9 Cooperatively Regulate Induction of Autophagy in Saccharomyces cerevisiae

2007 ◽  
Vol 18 (10) ◽  
pp. 4180-4189 ◽  
Author(s):  
Tomohiro Yorimitsu ◽  
Shadia Zaman ◽  
James R. Broach ◽  
Daniel J. Klionsky
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transcription Factors ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Signaling Pathways ◽  
Nutrient Sensing ◽  
Regulatory Mechanisms ◽  
Eukaryotic Cells ◽  
Tor Kinase ◽  
Kinase A

Autophagy is a highly conserved, degradative process in eukaryotic cells. The rapamycin-sensitive Tor kinase complex 1 (TORC1) has a major role in regulating induction of autophagy; however, the regulatory mechanisms are not fully understood. Here, we find that the protein kinase A (PKA) and Sch9 signaling pathways regulate autophagy cooperatively in yeast. Autophagy is induced in cells when PKA and Sch9 are simultaneously inactivated. Mutant alleles of these kinases bearing a mutation that confers sensitivity to the ATP-analogue inhibitor C3-1′-naphthyl-methyl PP1 revealed that autophagy was induced independently of effects on Tor kinase. The PKA–Sch9-mediated autophagy depends on the autophagy-related 1 kinase complex, which is also essential for TORC1-regulated autophagy, the transcription factors Msn2/4, and the Rim15 kinase. The present results suggest that autophagy is controlled by the signals from at least three partly separate nutrient-sensing pathways that include PKA, Sch9, and TORC1.

Fuel economy in food‐deprived skeletal muscle: signaling pathways and regulatory mechanisms

2007 ◽  
Vol 21 (13) ◽  
pp. 3431-3441 ◽  
Author(s):  
Pieter Lange ◽  
Maria Moreno ◽  
Elena Silvestri ◽  
Assunta Lombardi ◽  
Fernando Goglia ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Fuel Economy ◽  
Regulatory Mechanisms

scholarly journals Regeneration in sponge Sycon ciliatum mimics postlarval development

2020 ◽  
Author(s):  
Anael Soubigou ◽  
Ethan G Ross ◽  
Yousef Touhami ◽  
Nathan Chrismas ◽  
Vengamanaidu Modepalli
Keyword(s):  
Cell Culture ◽  
Signaling Pathways ◽  
High Throughput ◽  
Morphological Analysis ◽  
High Throughput Sequencing ◽  
Regulatory Mechanisms ◽  
Somatic Development ◽  
Developmental Signaling ◽  
Genetic Features ◽  
Comparative Transcriptomic Analysis

AbstractSomatic cells dissociated from an adult sponge can re-organize and develop into a functional juvenile. However, the extent to which regeneration recapitulates embryonic developmental signaling pathways has remained enigmatic for more than a century. To this end, we have standardized and established a sponge Sycon ciliatum regeneration protocol to achieve consistent regeneration in cell culture. From the morphological analysis, we demonstrated that dissociated sponge cells follow a series of morphological events resembling embryonic and postlarval development. Hence, we propose that sponge regeneration represents somatic development. To support our hypothesis, we performed high-throughput sequencing on regenerating samples and compared the data with regular embryonic and postlarval development of Sycon ciliatum. Our comparative transcriptomic analysis illuminates that sponge regeneration is equally as dynamic as embryogenesis. We find that sponge regeneration is orchestrated by complex regulatory mechanisms by recruiting signaling pathways like those utilized in embryonic development to organize into a functional juvenile. In the current study, we lay down the basic framework to study Sycon ciliatum regeneration. Since sponges are likely to be the first branch of extant multicellular animal and the sister lineage to nearly all animals, we suggest that this system can be explored to study the genetic features underlying the evolution of multicellularity and regeneration.

Sign in / Sign up

Export Citation Format

Share Document