Expanded: a gene involved in the control of cell proliferation in imaginal discs

Development ◽  
1993 ◽  
Vol 118 (4) ◽  
pp. 1291-1301 ◽  
Author(s):  
M. Boedigheimer ◽  
A. Laughon
Keyword(s):  
Cell Proliferation ◽  
Protein Interactions ◽  
Essential Gene ◽  
Spontaneous Mutation ◽  
Growth Control ◽  
Imaginal Discs ◽  
Apical Surface ◽  
Protein Protein Interactions ◽  
Acid Protein ◽  
Disc Cells

The expanded gene was first identified by a spontaneous mutation that causes broad wings. We have identified an enhancer-trap insertion within expanded and used it to generate additional mutations, including one null allele. expanded is an essential gene, necessary for proper growth control of imaginal discs and, when mutant, causes either hyperplasia or degeneration depending on the disc. Wing overgrowth in expanded hypermorphs is limited to specific regions along the anterior-posterior and dorsal-ventral axis. expanded encodes a novel 1429 amino acid protein that is localized to the apical surface of disc cells and contains three potential SH3-binding sites. Together, these observations suggest that the Expanded protein engages in protein-protein interactions regulating cell proliferation in discs.

Protein-Protein Interactions in the Tetraspanin Web

Physiology ◽  
2005 ◽  
Vol 20 (4) ◽  
pp. 218-224 ◽  
Author(s):  
Shoshana Levy ◽  
Tsipi Shoham
Keyword(s):  
Signal Transduction ◽  
Cell Proliferation ◽  
Protein Interactions ◽  
Membrane Microdomains ◽  
Protein Protein Interactions ◽  
Host Parasite Interactions ◽  
Evolutionarily Conserved ◽  
And Migration ◽  
Host Parasite ◽  
Partner Proteins

Tetraspanins are evolutionarily conserved membrane proteins that tend to associate laterally with one another and to cluster dynamically with numerous partner proteins in membrane microdomains. Consequently, members of this family are involved in the coordination of intracellular and intercellular processes, including signal transduction; cell proliferation, adhesion, and migration; cell fusion; and host-parasite interactions.

scholarly journals Network-Based Gene Expression Biomarkers for Cold and Heat Patterns of Rheumatoid Arthritis in Traditional Chinese Medicine

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Cheng Lu ◽  
Xuyan Niu ◽  
Cheng Xiao ◽  
Gao Chen ◽  
Qinglin Zha ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Cell Proliferation ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Protein Interactions ◽  
Acid Metabolism ◽  
Protein Protein Interactions ◽  
Significant Gene ◽  
Heat Pattern

In Traditional Chinese Medicine (TCM), patients with Rheumatoid Arthritis (RA) can be classified into two main patterns: cold-pattern and heat-pattern. This paper identified the network-based gene expression biomarkers for both cold- and heat-patterns of RA. Gene expression profilings of CD4+ T cells from cold-pattern RA patients, heat-pattern RA patients, and healthy volunteers were obtained using microarray. The differentially expressed genes and related networks were explored using DAVID, GeneSpring software, and the protein-protein interactions (PPI) method. EIF4A2, CCNT1, and IL7R, which were related to the up-regulation of cell proliferation and the Jak-STAT cascade, were significant gene biomarkers of the TCM cold pattern of RA. PRKAA1, HSPA8, and LSM6, which were related to fatty acid metabolism and the I-κB kinase/NF-κB cascade, were significant biomarkers of the TCM heat-pattern of RA. The network-based gene expression biomarkers for the TCM cold- and heat-patterns may be helpful for the further stratification of RA patients when deciding on interventions or clinical trials.

Changes in receptor location affect the ability of oxytocin to stimulate proliferative growth in prostate epithelial cells

2019 ◽  
Vol 31 (6) ◽  
pp. 1166 ◽  
Author(s):  
M. L. Gould ◽  
H. D. Nicholson
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cells ◽  
Cell Membrane ◽  
Lipid Rafts ◽  
Protein Interactions ◽  
Cell Signalling ◽  
Signalling Pathways ◽  
Protein Protein Interactions ◽  
Normal Prostate ◽  
Prostate Epithelial Cells

In normal prostate cells, cell membrane receptors are located within signalling microdomains called caveolae. During cancer progression, caveolae are lost and sequestered receptors move out onto lipid rafts. The aim of this study was to investigate whether a change in the localisation of receptors out of caveolae and onto the cell membrane increased cell proliferation invitro, and to determine whether this is related to changes in the cell signalling pathways. Normal human prostate epithelial cells (PrEC) and androgen-independent (PC3) cancer cells were cultured with 10nM dihydrotestosterone (DHT). The effects of oxytocin (OT) and gonadal steroids on proliferation were assessed using the MTS assay. Androgen receptor (AR) and oxytocin receptor (OTR) expression was identified by immunofluorescence and quantified by western blot. OTR and lipid raft staining was determined using Pearson’s correlation coefficient. Protein–protein interactions were detected and the cell signalling pathways identified. Treatment with OT did not affect the proliferation of PrEC. In PC3 cells, OT or androgen alone increased cell proliferation, but together had no effect. In normal cells, OTR localised to the membrane and AR localised to the nucleus, whereas in malignant cells both OTR and AR were identified in the cell membrane. Colocalisation of OTR and AR increased following treatment with androgens. Significantly fewer OTR/AR protein–protein interactions were seen in PrEC. With OT treatment, several cell signalling pathways were activated. Movement of OTR out of caveolae onto lipid rafts is accompanied by activation of alternative signal transduction pathways involved in stimulating increased cell proliferation.

scholarly journals Multiple change in E2F function and regulation occur upon muscle differentiation.

1995 ◽  
Vol 15 (4) ◽  
pp. 2252-2262 ◽  
Author(s):  
E K Shin ◽  
A Shin ◽  
C Paulding ◽  
B Schaffhausen ◽  
A S Yee
Keyword(s):  
Protein Interactions ◽  
Growth Control ◽  
Terminal Differentiation ◽  
Muscle Differentiation ◽  
Protein Protein Interactions ◽  
Protein Levels ◽  
Differentiated Cells ◽  
Prominent Component ◽  
Undifferentiated Cells ◽  
E2f Transcription Factor

We have examined regulation of the E2F transcription factor during differentiation of muscle cells. E2F regulates many genes involved in growth control and is also the target of regulation by diverse cellular signals, including the RB family of growth suppressors (e.g., the retinoblastoma protein [RB], p107, and p130). The following aspects of E2F function and regulation during muscle differentiation were investigated: (i) protein-protein interactions, (ii) protein levels, (iii) phosphorylation of the E2F protein, and (iv) transcriptional activity. A distinct E2F complex was present in differentiated cells but not in undifferentiated cells. The p130 protein was a prominent component of the E2F complex associated with differentiation. In contrast, in undifferentiated cells, the p107 protein was the prominent component in one of three E2F complexes. In addition, use of a differentiation-defective muscle line provided genetic and biochemical evidence that quiescence and differentiation are separable events. Exclusive formation of the E2F-p130 complex did not occur in this differentiation-defective line; however, E2F complexes diagnostic of quiescence were readily apparent. Thus, sole formation of the E2F-p130 complex is a necessary event in terminal differentiation. Other changes in E2F function and regulation upon differentiation include decreased phosphorylation and increased repression by E2F. These observations suggest that the regulation of E2F function during terminal differentiation may proceed through differential interaction within the RB family and/or phosphorylation.

scholarly journals Structural Determinants and Proliferative Consequences of Connexin 37 Hemichannel Function in Insulinoma Cells

2014 ◽  
Vol 289 (44) ◽  
pp. 30379-30386 ◽  
Author(s):  
Miranda E. Good ◽  
José F. Ek-Vitorín ◽  
Janis M. Burt
Keyword(s):  
Cell Proliferation ◽  
Protein Interactions ◽  
Published Data ◽  
Cancer Cell Proliferation ◽  
Intercellular Signaling ◽  
Protein Protein Interactions ◽  
Structural Determinants ◽  
C Terminus ◽  
Insulinoma Cells ◽  
Rat Insulinoma

Connexin (Cx) 37 suppresses vascular and cancer cell proliferation. The C terminus and a channel able to function are necessary, and neither by itself is sufficient, for Cx37 to mediate growth suppression. Cx37 supports transmembrane and intercellular signaling by forming functional hemichannels (HCs) and gap junction channels (GJCs), respectively. Here we determined whether Cx37 with HC, but not GJC, functionality would suppress proliferation of rat insulinoma (Rin) cells comparably to wild-type Cx37 (Cx37-WT). We mutated extracellular loop residues hypothesized to compromise HC docking but not HC function (six cysteines mutated to alanine, C54A,C61A,C65A, C187A,C192A,C198A (designated as C6A); N55I; and Q58L). All three mutants trafficked to the plasma membrane and formed protein plaques comparably to Cx37-WT. None of the mutants formed functional GJCs, and Cx37-C6A did not form functional HCs. Cx37-N55I and -Q58L formed HCs with behavior and permeation properties similar to Cx37-WT (especially Q58L), but none of the mutants suppressed Rin cell proliferation. The data indicate that determinants of Cx37 HC function differ from other Cxs and that HC functions with associated HC-supported protein-protein interactions are not sufficient for Cx37 to suppress Rin cell proliferation. Together with previously published data, these results suggest that Cx37 suppresses Rin cell proliferation only when in a specific conformation achieved by interaction of the C terminus with a Cx37 pore-forming domain able to open as a GJC.

scholarly journals Evolution of KIPPIS as a versatile platform for evaluating intracellularly functional peptide aptamers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daiki Kashima ◽  
Masahiro Kawahara
Keyword(s):  
Cell Proliferation ◽  
Protein Interactions ◽  
Detection Sensitivity ◽  
Chimeric Proteins ◽  
Dependent Manner ◽  
Protein Protein Interactions ◽  
Small Peptides ◽  
Peptide Aptamers ◽  
Peptide Aptamer ◽  
Functional Peptide

AbstractChimeric proteins have been widely used to evaluate intracellular protein–protein interactions (PPIs) in living cells with various readouts. By combining an interleukin-3-dependent murine cells and chimeric proteins containing a receptor tyrosine kinase c-kit, we previously established a c-kit-based PPI screening (KIPPIS) system to evaluate and select protein binders. In the KIPPIS components, proteins of interest are connected with a chemically inducible helper module and the intracellular domain of the growth-signaling receptor c-kit, which detects PPIs based on cell proliferation as a readout. In this system, proteins of interest can be incorporated into chimeric proteins without any scaffold proteins, which would be advantageous for evaluating interaction between small peptides/domains. To prove this superiority, we apply KIPPIS to 6 peptide aptamer–polypeptide pairs, which are derived from endogenous, synthetic, and viral proteins. Consequently, all of the 6 peptide aptamer–polypeptide interactions are successfully detected by cell proliferation. The detection sensitivity can be modulated in a helper ligand-dependent manner. The assay results of KIPPIS correlate with the activation levels of Src, which is located downstream of c-kit-mediated signal transduction. Control experiments reveal that KIPPIS clearly discriminates interacting aptamers from non-interacting ones. Thus, KIPPIS proves to be a versatile platform for evaluating the binding properties of peptide aptamers.

scholarly journals Synthesis of Novel Suramin Analogs With Anti-Proliferative Activity via FGF1 and FGFRD2 Blockade

2022 ◽  
Vol 9 ◽  
Author(s):  
Nuzhat Parveen ◽  
Yan-Liang Lin ◽  
Ruey-Hwang Chou ◽  
Chung-Ming Sun ◽  
Chin Yu
Keyword(s):  
Cell Proliferation ◽  
Protein Interactions ◽  
Binding Sites ◽  
Proliferative Activity ◽  
Three Dimensional ◽  
Cancer Cell Line ◽  
Protein Protein Interactions ◽  
Docking Simulations ◽  
Three Dimensional Models

A promising approach in cancer therapy is the inhibition of cell proliferation using small molecules. In this study, we report the synthesis of suramin derivatives and their applications. We used NMR spectroscopy and docking simulations to confirm binding sites and three-dimensional models of the ligand-protein complex. The WST-1 assay was used to assess cell viability and cell proliferation in vitro to evaluate the inhibition of protein–protein interactions and to investigate the anti-proliferative activities in a breast cancer cell line. All the suramin derivatives showed anti-proliferative activity by blocking FGF1 binding to its receptor FGFRD2. The dissociation constant was measured by fluorescence spectroscopy. The suramin compound derivatives synthesized herein show potential as novel therapeutic agents for their anti-proliferative activity via the inhibition of protein–protein interactions. The cytotoxicity of these suramin derivatives was lower than that of the parent suramin compound, which may be considered a significant advancement in this field. Thus, these novel suramin derivatives may be considered superior anti-metastasis molecules than those of suramin.

scholarly journals Pseudokinases: From Allosteric Regulation of Catalytic Domains and the Formation of Macromolecular Assemblies to Emerging Drug Targets

Catalysts ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 778 ◽  
Author(s):  
Andrada Tomoni ◽  
Jonathan Lees ◽  
Andrés G. Santana ◽  
Victor M. Bolanos-Garcia ◽  
Agatha Bastida
Keyword(s):  
Cell Proliferation ◽  
Protein Interactions ◽  
Drug Targets ◽  
Structural Features ◽  
Therapeutic Window ◽  
Amino Acid Residues ◽  
Protein Protein Interactions ◽  
Therapeutic Approaches ◽  
Macromolecular Assemblies ◽  
Catalytic Domains

Pseudokinases are a member of the kinase superfamily that lack one or more of the canonical residues required for catalysis. Protein pseudokinases are widely distributed across species and are present in proteins that perform a great diversity of roles in the cell. They represent approximately 10% to 40% of the kinome of a multicellular organism. In the human, the pseudokinase subfamily consists of approximately 60 unique proteins. Despite their lack of one or more of the amino acid residues typically required for the productive interaction with ATP and metal ions, which is essential for the phosphorylation of specific substrates, pseudokinases are important functional molecules that can act as dynamic scaffolds, competitors, or modulators of protein–protein interactions. Indeed, pseudokinase misfunctions occur in diverse diseases and represent a new therapeutic window for the development of innovative therapeutic approaches. In this contribution, we describe the structural features of pseudokinases that are used as the basis of their classification; analyse the interactome space of human pseudokinases and discuss their potential as suitable drug targets for the treatment of various diseases, including metabolic, neurological, autoimmune, and cell proliferation disorders.

scholarly journals Downstream and Intermediate Interactions of Synovial Sarcoma-Associated Fusion Oncoproteins and Their Implication for Targeted Therapy

Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Joanna Przybyl ◽  
Monika Jurkowska ◽  
Piotr Rutkowski ◽  
Maria Debiec-Rychter ◽  
Janusz A. Siedlecki
Keyword(s):  
Cell Proliferation ◽  
Targeted Therapy ◽  
Synovial Sarcoma ◽  
Chromatin Remodeling ◽  
Protein Interactions ◽  
Fusion Proteins ◽  
Soft Tissue Tumor ◽  
Fusion Genes ◽  
Protein Protein Interactions ◽  
Tp53 Pathway

Synovial sarcoma (SS), an aggressive type of soft tissue tumor, occurs mostly in adolescents and young adults. The origin and molecular mechanism of the development of SS remain only partially known. Over 90% of SS cases are characterized by the t(X;18)(p11.2;q11.2) translocation, which results mainly in the formation ofSS18-SSX1orSS18-SSX2fusion genes. In recent years, several reports describing direct and indirect interactions ofSS18-SSX1/SSX2oncoproteins have been published. These reports suggest that the fusion proteins particularly affect the cell growth, cell proliferation, TP53 pathway, and chromatin remodeling mechanisms, contributing to SS oncogenesis. Additional research efforts are required to fully explore the protein-protein interactions of SS18-SSX oncoproteins and the pathways that are regulated by these partnerships for the development of effective targeted therapy.

scholarly journals BP180/Collagen XVII: A Molecular View

2021 ◽  
Vol 22 (22) ◽  
pp. 12233
Author(s):  
Jussi Tuusa ◽  
Nina Kokkonen ◽  
Kaisa Tasanen
Keyword(s):  
Cell Proliferation ◽  
Protein Interactions ◽  
Transmembrane Protein ◽  
Epidermal Keratinocytes ◽  
Central Component ◽  
Type I ◽  
Type Ii ◽  
Protein Protein Interactions ◽  
Collagen Xvii ◽  
Biochemical Features

BP180 is a type II collagenous transmembrane protein and is best known as the major autoantigen in the blistering skin disease bullous pemphigoid (BP). The BP180 trimer is a central component in type I hemidesmosomes (HD), which cause the adhesion between epidermal keratinocytes and the basal lamina, but BP180 is also expressed in several non-HD locations, where its functions are poorly characterized. The immunological roles of intact and proteolytically processed BP180, relevant in BP, have been subject to intensive research, but novel functions in cell proliferation, differentiation, and aging have also recently been described. To better understand the multiple physiological functions of BP180, the focus should return to the protein itself. Here, we comprehensively review the properties of the BP180 molecule, present new data on the biochemical features of its intracellular domain, and discuss their significance with regard to BP180 folding and protein–protein interactions.

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