Erythropoietin and co.: intrinsic structure and functional disorder

2017 ◽  
Vol 13 (1) ◽  
pp. 56-72 ◽  
Author(s):  
Vladimir N. Uversky ◽  
Elrashdy M. Redwan
Keyword(s):  
Growth Factor ◽  
Intrinsic Disorder ◽  
Biological Processes ◽  
Functional Disorder ◽  
Intrinsic Structure

Erythropoietin (Epo) is a glycoprotein with important roles in erythropoiesis and other biological processes by serving as a hormone, a cytokine, or a growth factor. At least in part, the Epo multifunctionality is driven by its partners. The goal of this article is to evaluate the roles of intrinsic disorder in the functions of Epo and its primary interactors, EpoR, βCR, and HIF-1α.

scholarly journals Nuclear Functions of TOR: Impact on Transcription and the Epigenome

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 641 ◽  
Author(s):  
R. Nicholas Laribee ◽  
Ronit Weisman
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Protein Kinase ◽  
Neurological Disorders ◽  
Regulation Of Gene Expression ◽  
Clinical Implications ◽  
Biological Processes ◽  
The Core ◽  
Regulation Of Metabolism ◽  
Pharmacological Target

The target of rapamycin (TOR) protein kinase is at the core of growth factor- and nutrient-dependent signaling pathways that are well-known for their regulation of metabolism, growth, and proliferation. However, TOR is also involved in the regulation of gene expression, genomic and epigenomic stability. TOR affects nuclear functions indirectly through its activity in the cytoplasm, but also directly through active nuclear TOR pools. The mechanisms by which TOR regulates its nuclear functions are less well-understood compared with its cytoplasmic activities. TOR is an important pharmacological target for several diseases, including cancer, metabolic and neurological disorders. Thus, studies of the nuclear functions of TOR are important for our understanding of basic biological processes, as well as for clinical implications.

scholarly journals The MAP4K4-STRIPAK complex promotes growth and tissue invasion in medulloblastoma

2021 ◽  
Author(s):  
Jessica Migliavacca ◽  
Buket Zuellig ◽  
Charles Capdeville ◽  
Michael Andreas Grotzer ◽  
Martin Baumgartner
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Target Gene ◽  
Biological Processes ◽  
Precise Control ◽  
Target Gene Expression ◽  
Tissue Invasion ◽  
Proliferative Effect ◽  
Pathway Regulation ◽  
The Brain

Proliferation and motility are mutually exclusive biological processes associated with cancer that depend on precise control of upstream signaling pathways with overlapping functionalities. We find that STRN3 and STRN4 scaffold subunits of the STRIPAK complex interact with MAP4K4 for pathway regulation in medulloblastoma. Disruption of the MAP4K4-STRIPAK complex impairs growth factor-induced migration and tissue invasion and stalls YAP/TAZ target gene expression and oncogenic growth. The migration promoting functions of the MAP4K4-STRIPAK complex involve the activation of novel PKCs and the phosphorylation of the membrane targeting S157 residue of VASP through MAP4K4. The anti-proliferative effect of complex disruption is associated with reduced YAP/TAZ target gene expression and results in repressed tumor growth in the brain tissue. This dichotomous functionality of the STRIPAK complex in migration and proliferation control acts through MAP4K4 regulation in tumor cells and provides relevant mechanistic insights into novel tumorigenic functions of the STRIPAK complex in medulloblastoma.

scholarly journals Continuous variable response, kinetic gating and connectivity that govern IS topology are perturbed in hyperinsulinemia

2020 ◽  
Author(s):  
Namrata Shukla ◽  
Shantanu Kadam ◽  
Ranjith Padinhateeri ◽  
Ullas Kolthur-Seetharam
Keyword(s):  
Growth Factor ◽  
Continuous Variable ◽  
Kinetic Control ◽  
Biological Processes ◽  
Fasting Insulin ◽  
Variable Response ◽  
Variable Parameters ◽  
Simulation Based ◽  
Novel Therapeutic Strategies ◽  
Almost All

AbstractUnderstanding kinetic control of biological processes is as important as identifying components that constitute pathways. Insulin-signaling (IS) is central for almost all metazoans and its perturbations are associated with various diseases and aging. While temporal phosphorylation changes and kinetic constants have provided some insights, constant or variable parameters that establish and maintain signal topology are poorly understood. Our iterative experimental and mathematical simulation-based approaches reveal novel kinetic parameters that encode concentration and nutrient dependent information. Further, we find that pulsatile fasting insulin rewires IS akin to memory and in anticipation of a fed response. Importantly, selective kinetic gating of signals and maximum connectivity, between metabolic and growth-factor arms under normo-insulinemic states, maintains network topology. In addition to unraveling kinetic constraints that determine cascade architecture, our findings will help in identifying novel therapeutic strategies that conserve coupling between metabolic and growth-factor arms, which is lost in diseases and conditions of hyperinsulinemia.

Exploration of Human Xylosyltransferase for Chemoenzymatic Synthesis of Proteoglycan Linkage Region

2021 ◽  
Author(s):  
Jia Gao ◽  
Po-han Lin ◽  
Setare Tahmasebi Nick ◽  
Kunli Liu ◽  
Kefei Yu ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Growth Factor ◽  
Tumor Progression ◽  
Chemoenzymatic Synthesis ◽  
Biological Processes ◽  
Linkage Region ◽  
The Core ◽  
Core Proteins ◽  
Regulation Of Growth

Proteoglycans (PGs) play important roles in many biological processes including tumor progression, cell adhesion, and regulation of growth factor activities. With glycosaminoglycan chains attached to the core proteins in nature,...

scholarly journals Functional Anthology of Intrinsic Disorder. 1. Biological Processes and Functions of Proteins with Long Disordered Regions

2007 ◽  
Vol 6 (5) ◽  
pp. 1882-1898 ◽  
Author(s):  
Hongbo Xie ◽  
Slobodan Vucetic ◽  
Lilia M. Iakoucheva ◽  
Christopher J. Oldfield ◽  
A. Keith Dunker ◽  
...  
Keyword(s):  
Intrinsic Disorder ◽  
Biological Processes ◽  
Disordered Regions

scholarly journals The Cellular Senescence-Inhibited Gene Is Essential for PPM1A Myristoylation To Modulate Transforming Growth Factor β Signaling

2018 ◽  
Vol 38 (23) ◽  
Author(s):  
Feng Zhu ◽  
Nan Xie ◽  
Zhe Jiang ◽  
Guodong Li ◽  
Liwei Ma ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phosphatase Activity ◽  
Cellular Senescence ◽  
Protein Phosphatase ◽  
Transforming Growth Factor ◽  
Regulatory Mechanism ◽  
Biological Significance ◽  
Transforming Growth Factor Β ◽  
Biological Processes ◽  
New Ideas

ABSTRACT The cellular senescence-inhibited gene (CSIG) is implicated in important biological processes, including cellular senescence and apoptosis. Our work showed that CSIG is involved in the myristoylation of the serine/threonine protein phosphatase PPM1A. Previous research has shown that myristoylation is necessary for PPM1A to dephosphorylate Smad2 and Smad3. However, the control and the biological significance of the myristoylation remain poorly understood. In this study, we found that CSIG knockdown disturbs PPM1A myristoylation and reduces the dephosphorylation by PPM1A of its substrate Smad2. By regulating PPM1A myristoylation, CSIG is involved in modulating the signaling of transforming growth factor β (TGF-β). Further study of the mechanism indicated that CSIG facilitates the interaction between N-myristoyltransferase 1 (NMT1) and PPM1A. Taking the data together, we found that CSIG is a regulator of PPM1A myristoylation and TGF-β signaling. By promoting the myristoylation of PPM1A, CSIG enhanced the phosphatase activity of PPM1A and further inhibited TGF-β signaling. This work not only extends the biological significance of CSIG but also provides new ideas and a reference for the study of the regulatory mechanism of myristoylation.

scholarly journals Expression level of long non-coding RNA colon adenocarcinoma hypermethylated serve as a novel prognostic biomarker in patients with thyroid carcinoma

2021 ◽  
Author(s):  
Yong Xiao ◽  
Youbing Tu ◽  
Yuantao Li
Keyword(s):  
Cell Adhesion ◽  
Growth Factor ◽  
Thyroid Carcinoma ◽  
Signaling Pathways ◽  
Rna Sequencing ◽  
Growth Factor Receptor ◽  
Enrichment Analysis ◽  
Biological Processes ◽  
Connectivity Map ◽  
Function Enrichment

This study attempts to identify the prognostic value and potential mechanism of action of colorectal adenocarcinoma hypermethylated(CAHM) in thyroid carcinoma(THCA) by using the RNA sequencing dataset from The Cancer Genome Atlas(TCGA). The functional mechanism of CAHM was explored by using RNA sequencing dataset and multiple functional enrichment analysis approaches. Connectivity map online analysis tool was also used to predict CAHM targeted drugs. Survival analysis suggests that THCA patients with high CAHM expression have lower risk of death than these low CAHM expression(Log-rank P=0.022, adjusted P=0.011, HR=0.187, 95%CI=0.051-0.685). Function enrichment of CAHM co-expression genes suggests that CAHM may play a role in the following biological processes: DNA repair, cell adhesion, DNA replication, vascular endothelial growth factor receptor, Erb-B2 receptor tyrosine kinase 2, ErbB and thyroid hormone signaling pathways. Function enrichment of DEGs between low- and high-CAHM phenotype suggests that different CAHM expression levels may have the following differences in biological processes in THCA: cell adhesion, cell proliferation, extracellular signal regulated kinase 1(ERK1) and ERK2 cascade, G-protein coupled receptor, chemokine, and phosphatidylinositol-3-kinase-Akt signaling pathways. Connectivity map have identified five drugs (levobunolol, NU-1025, quipazine, anisomycin and sulfathiazole) for CAHM targeted therapy in THCA. Gene set enrichment analysis suggest that low CAHM phenotype were notably enriched in p53, nuclear factor kappa B, Janus kinase-signal transducer and activators of transcription, tumor necrosis factor, epidermal growth factor receptor and other signaling pathways. In the present study, we have identified CAHM may be serve as a novel prognostic biomarkers for predicting overall survival in patients with THCA.

scholarly journals Structural biology of the TGFβ family

2019 ◽  
Vol 244 (17) ◽  
pp. 1530-1546 ◽  
Author(s):  
Erich J Goebel ◽  
Kaitlin N Hart ◽  
Jason C McCoy ◽  
Thomas B Thompson
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Structural Biology ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Biological Processes ◽  
Tgfβ Signaling ◽  
Growth Factor Beta ◽  
Tgfβ Signaling Pathway

The transforming growth factor beta (TGFβ) signaling pathway orchestrates a wide breadth of biological processes, ranging from bone development to reproduction. Given this, there has been a surge of interest from the drug development industry to modulate the pathway – at several points. This review discusses and provides additional context for several layers of the TGFβ signaling pathway from a structural biology viewpoint. The combination of structural techniques coupled with biophysical studies has provided a foundational knowledge of the molecular mechanisms governing this high impact, ubiquitous pathway, underlying many of the current therapeutic pursuits. This work seeks to consolidate TGFβ-related structural knowledge and educate other researchers of the apparent gaps that still prove elusive. We aim to highlight the importance of these structures and provide the contextual information to understand the contribution to the field, with the hope of advancing the discussion and exploration of the TGFβ signaling pathway. Impact statement The transforming growth factor beta (TGFβ) signaling pathway is a multifacetted and highly regulated pathway, forming the underpinnings of a large range of biological processes. Here, we review and consolidate the key steps in TGFβ signaling using literature rooted in structural and biophysical techniques, with a focus on molecular mechanisms and gaps in knowledge. From extracellular regulation to ligand–receptor interactions and intracellular activation cascades, we hope to provide an introductory base for understanding the TGFβ pathway as a whole.

Quantitatively Mapping the Interaction of HER2 and EGFR on Cell Membranes with Peptide Probes

Nanoscale ◽  
2021 ◽  
Author(s):  
Qiuyan Yan ◽  
Mingjun Cai ◽  
Yingying Jing ◽  
Hongru Li ◽  
Haijiao Xu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Biological Processes ◽  
Her Family ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth ◽  
Peptide Probes

Human epidermal growth factor receptor-2 (HER2) is a member of the epidermal growth factor receptor (HER) family that involved in various biological processes such as cell proliferation, survival, differentiation, migration...

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