scholarly journals Exploring the role of the MLL1 complex in leukemia by small molecule targeting of an essential protein‐protein interaction

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Elizabeth Townsend ◽  
Yali Dou
Keyword(s):  
Small Molecule ◽  
Protein Interaction ◽  
Essential Protein ◽  
Protein Protein Interaction

scholarly journals Development of a Novel High-Throughput Screen and Identification of Small-Molecule Inhibitors of the Gα–RGS17 Protein–Protein Interaction Using AlphaScreen

2011 ◽  
Vol 16 (8) ◽  
pp. 869-877 ◽  
Author(s):  
Duncan I. Mackie ◽  
David L. Roman
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
Protein Interaction ◽  
High Throughput Screening ◽  
Drug Targets ◽  
Screening Method ◽  
Fold Increase ◽  
Rgs Proteins ◽  
High Throughput Screen ◽  
Protein Protein Interaction

In this study, the authors used AlphaScreen technology to develop a high-throughput screening method for interrogating small-molecule libraries for inhibitors of the Gαo–RGS17 interaction. RGS17 is implicated in the growth, proliferation, metastasis, and the migration of prostate and lung cancers. RGS17 is upregulated in lung and prostate tumors up to a 13-fold increase over patient-matched normal tissues. Studies show RGS17 knockdown inhibits colony formation and decreases tumorigenesis in nude mice. The screen in this study uses a measurement of the Gαo–RGS17 protein–protein interaction, with an excellent Z score exceeding 0.73, a signal-to-noise ratio >70, and a screening time of 1100 compounds per hour. The authors screened the NCI Diversity Set II and determined 35 initial hits, of which 16 were confirmed after screening against controls. The 16 compounds exhibited IC50 <10 µM in dose–response experiments. Four exhibited IC50 values <6 µM while inhibiting the Gαo–RGS17 interaction >50% when compared to a biotinylated glutathione-S-transferase control. This report describes the first high-throughput screen for RGS17 inhibitors, as well as a novel paradigm adaptable to many other RGS proteins, which are emerging as attractive drug targets for modulating G-protein-coupled receptor signaling.

scholarly journals Regulation of clathrin coat assembly by Eps15 homology domain–mediated interactions during endocytosis

2012 ◽  
Vol 23 (4) ◽  
pp. 687-700 ◽  
Author(s):  
Ryohei Suzuki ◽  
Junko Y. Toshima ◽  
Jiro Toshima
Keyword(s):  
Functional Diversity ◽  
Protein Interaction ◽  
Interaction Domain ◽  
Protein Protein Interaction ◽  
Molecular Events ◽  
Biological Studies ◽  
Eh Domain ◽  
Actin Patch ◽  
Lines Of Evidence

Clathrin-mediated endocytosis involves a coordinated series of molecular events regulated by interactions among a variety of proteins and lipids through specific domains. One such domain is the Eps15 homology (EH) domain, a highly conserved protein–protein interaction domain present in a number of proteins distributed from yeast to mammals. Several lines of evidence suggest that the yeast EH domain–containing proteins Pan1p, End3p, and Ede1p play important roles during endocytosis. Although genetic and cell-biological studies of these proteins suggested a role for the EH domains in clathrin-mediated endocytosis, it was unclear how they regulate clathrin coat assembly. To explore the role of the EH domain in yeast endocytosis, we mutated those of Pan1p, End3p, or Ede1p, respectively, and examined the effects of single, double, or triple mutation on clathrin coat assembly. We found that mutations of the EH domain caused a defect of cargo internalization and a delay of clathrin coat assembly but had no effect on assembly of the actin patch. We also demonstrated functional redundancy among the EH domains of Pan1p, End3p, and Ede1p for endocytosis. Of interest, the dynamics of several endocytic proteins were differentially affected by various EH domain mutations, suggesting functional diversity of each EH domain.

scholarly journals Analysis of origin and protein-protein interaction maps suggests distinct oncogenic role of nuclear EGFR during cancer evolution

2017 ◽  
Vol 8 (5) ◽  
pp. 903-912 ◽  
Author(s):  
Ainur Sharip ◽  
Diyora Abdukhakimova ◽  
Xiao Wang ◽  
Alexey Kim ◽  
Yevgeniy Kim ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Cancer Evolution ◽  
Protein Protein Interaction

scholarly journals The role of exon shuffling in shaping protein-protein interaction networks

BMC Genomics ◽  
2010 ◽  
Vol 11 (Suppl 5) ◽  
pp. S11 ◽  
Author(s):  
Douglas V Cancherini ◽  
Gustavo S França ◽  
Sandro J de Souza
Keyword(s):  
Protein Interaction ◽  
Protein Interaction Networks ◽  
Interaction Networks ◽  
Exon Shuffling ◽  
Protein Protein Interaction ◽  
Protein Protein Interaction Networks

Probing the Small-Molecule Inhibition of an Anticancer Therapeutic Protein-Protein Interaction Using a Solid-State Nanopore

2016 ◽  
Vol 128 (19) ◽  
pp. 5807-5811 ◽  
Author(s):  
Dong-Kyu Kwak ◽  
Hongsik Chae ◽  
Mi-Kyung Lee ◽  
Ji-Hyang Ha ◽  
Gaurav Goyal ◽  
...  
Keyword(s):  
Solid State ◽  
Small Molecule ◽  
Protein Interaction ◽  
Therapeutic Protein ◽  
Protein Protein Interaction ◽  
Small Molecule Inhibition
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