Biological Sequence Motif Discovery Using <i>motif‐x</i>

Chou, Michael F.; Schwartz, Daniel

doi:10.1002/0471250953.bi1315s35

Cited by 345 publications

(370 citation statements)

References 20 publications

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“…20,21 Using these data sets as the input, there was a single AxK motif that was identified in the full data set (n ¼ 131, Po1e-6; Figure 4A) and the statistically significant data set (n ¼ 67, Po1e-5; Figure 4B). At the time of this publication, it is believed that this Figure 2.…”

Section: Resultsmentioning

confidence: 99%

Characterization of the Ubiquitin-Modified Proteome Regulated by Transient Forebrain Ischemia

Iseki

Sheng

Thompson³

et al. 2013

J Cereb Blood Flow Metab

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Ubiquitylation is a posttranslational protein modification that modulates various cellular processes of key significance, including protein degradation and DNA damage repair. In animals subjected to transient cerebral ischemia, ubiquitin-conjugated proteins accumulate in Triton-insoluble aggregates. Although this process is widely considered to modulate the fate of postischemic neurons, few attempts have been made to characterize the ubiquitin-modified proteome in these aggregates. We performed proteomics analyses to identify ubiquitylated proteins in postischemic aggregates. Mice were subjected to 10 minutes of forebrain ischemia and 4 hours of reperfusion. The hippocampi were dissected, aggregates were isolated, and trypsin-digested after spiking with GG-BSA as internal standard. K-e-GG-containing peptides were immunoprecipitated and analyzed by label-free quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. We identified 1,664 peptides to 520 proteins containing at least one K-e-GG. Sixty-six proteins were highly ubiquitylated, with 10 or more K-e-GG peptides. Based on selection criteria of greater than fivefold increase and Po0.001, 763 peptides to 272 proteins were highly enriched in postischemic aggregates. These included proteins involved in important neuronal functions and signaling pathways that are impaired after ischemia. Results of this study could serve as an important platform to uncover the mechanisms linking insoluble ubiquitin aggregates to the functions of postischemic neurons.

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Section: Resultsmentioning

confidence: 99%

Characterization of the Ubiquitin-Modified Proteome Regulated by Transient Forebrain Ischemia

Iseki

Sheng

Thompson³

et al. 2013

J Cereb Blood Flow Metab

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“…Enrichment of amino acid motifs was determined with MotifX software (Chou and Schwartz, 2011) and plotted using WebLogo (Crooks et al, 2004), and associated kinases were assigned with the NetPhorest algorithm (Miller et al, 2008).…”

Section: Methodsmentioning

confidence: 99%

G Protein–Coupled Receptor Endocytosis Confers Uniformity in Responses to Chemically Distinct Ligands

Tsvetanova

Trester-Zedlitz²,

Newton³

et al. 2016

Mol Pharmacol

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The ability of chemically distinct ligands to produce different effects on the same G protein-coupled receptor (GPCR) has interesting therapeutic implications, but, if excessively propagated downstream, would introduce biologic noise compromising cognate ligand detection. We asked whether cells have the ability to limit the degree to which chemical diversity imposed at the ligand-GPCR interface is propagated to the downstream signal. We carried out an unbiased analysis of the integrated cellular response elicited by two chemically and pharmacodynamically diverse b-adrenoceptor agonists, isoproterenol and salmeterol. We show that both ligands generate an identical integrated response, and that this stereotyped output requires endocytosis. We further demonstrate that the endosomal b2-adrenergic receptor signal confers uniformity on the downstream response because it is highly sensitive and saturable. Based on these findings, we propose that GPCR signaling from endosomes functions as a biologic noise filter to enhance reliability of cognate ligand detection.

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“…Abundances of motifs for Asc1p-dependently regulated phosphosites were compared to the occurrences of the same motifs for all phosphosites identified in this study. Motifs were searched for sites with localization probabilities of Ն0.75 by using motif-x software (49,50). Additional motifs identified for the complete proteome are not depicted.…”

Section: Figmentioning

confidence: 99%

Asc1p/RACK1 Connects Ribosomes to Eukaryotic Phosphosignaling

Schmitt

Smolinski

Neumann

et al. 2017

Molecular and Cellular Biology

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WD40 repeat proteins fold into characteristic ␤-propeller structures and control signaling circuits during cellular adaptation processes within eukaryotes. The RACK1 protein of Saccharomyces cerevisiae, Asc1p, consists exclusively of a single sevenbladed ␤-propeller that operates from the ribosomal base at the head region of the 40S subunit. Here we show that the R38D K40E ribosomal binding-compromised variant (Asc1DEp) is severely destabilized through mutation of phosphosite T143 to a dephosphorylation-mimicking alanine, probably through proteasomal degradation, leading to asc1 Ϫ phenotypes. Phosphosite Y250 contributes to resistance to translational inhibitors but does not influence Asc1DEp stability. Beyond its own phosphorylation at T143, Y250, and other sites, Asc1p heavily influences the phosphorylation of as many as 90 proteins at 120 sites. Many of these proteins are regulators of fundamental processes ranging from mRNA translation to protein transport and turnover, cytoskeleton organization, and cellular signaling. Our data expose Asc1p/ RACK1 as a key factor in phosphosignaling and manifest it as a control point at the head of the ribosomal 40S subunit itself regulated through posttranslational modification.

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Biological Sequence Motif Discovery Using motif‐x

Cited by 345 publications

References 20 publications

Characterization of the Ubiquitin-Modified Proteome Regulated by Transient Forebrain Ischemia

Characterization of the Ubiquitin-Modified Proteome Regulated by Transient Forebrain Ischemia

G Protein–Coupled Receptor Endocytosis Confers Uniformity in Responses to Chemically Distinct Ligands

Asc1p/RACK1 Connects Ribosomes to Eukaryotic Phosphosignaling

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