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13 Publications visible to you, out of a total of 13
A Mechanistic, Model-Based Approach to Safety Assessment in Clinical Development

Abstract

Not specified

Editor:

Date Published: 2013

Publication Type: Not specified

Semantic Data and Models Sharing in Systems Biology: The Just Enough Results Model and the SEEK Platform

Abstract

Not specified

Authors: Katherine Wolstencroft, Stuart Owen, Olga Krebs, Wolfgang Mueller, Quyen Nguyen, Jacky L. Snoep, Carole Goble

Date Published: 2013

Publication Type: Not specified

Inferring statin-induced gene regulatory relationships in primary human hepatocytes

Abstract (Expand)

MOTIVATION: Statins are the most widely used cholesterol-lowering drugs. The primary target of statins is HMG-CoA reductase, a key enzyme in cholesterol synthesis. However, statins elicit pleitropic … responses including beneficial as well as adverse effects in the liver or other organs. Today, the regulatory mechanisms that cause these pleiotropic effects are not sufficiently understood. RESULTS: In this work, genome-wide RNA expression changes in primary human hepatocytes of six individuals were measured at up to six time points upon atorvastatin treatment. A computational analysis workflow was applied to reconstruct regulatory mechanisms based on these drug-response data and available knowledge about transcription factor (TF) binding specificities and protein-drug interactions. Several previously unknown TFs were predicted to be involved in atorvastatin-responsive gene expression. The novel relationships of nuclear receptors NR2C2 and PPARA on CYP3A4 were successfully validated in wet-lab experiments. AVAILABILITY: Microarray data are available at the Gene Expression Omnibus (GEO) database at www.ncbi.nlm.nih.gov/geo/, under accession number GSE29868. CONTACT: andreas.zell@uni-tuebingen.de; adrian.schroeder@uni-tuebingen.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Authors: A. Schroder, J. Wollnik, C. Wrzodek, A. Drager, M. Bonin, O. Burk, M. Thomas, W. E. Thasler, U. M. Zanger, A. Zell

Date Published: 14th Jul 2011

Publication Type: Not specified

Inferring statin-induced gene regulatory relationships in primary human hepatocytes

Abstract

Not specified

Authors: A. Schroder, J. Wollnik, C. Wrzodek, A. Drager, M. Bonin, O. Burk, M. Thomas, W. E. Thasler, U. M. Zanger, A. Zell

Date Published: 14th Jul 2011

Publication Type: Not specified

Identification and characterization of the PhhR regulon in Pseudomonas putida

Abstract

Not specified

Authors: M. Carmen Herrera, Estrella Duque, José J. Rodríguez-Herva, Ana M. Fernández-Escamilla, Juan L. Ramos

Date Published: 2010

Publication Type: Not specified

Cypher, a striated muscle-restricted PDZ and LIM domain-containing protein, binds to alpha-actinin-2 and protein kinase C

Abstract (Expand)

We have cloned and characterized a novel striated muscle-restricted protein (Cypher) that has two mRNA splice variants, designated Cypher1 and Cypher2. Both proteins contain an amino-terminal PDZ domain. … Cypher1, but not Cypher2, contains three carboxyl-terminal LIM domains and an amino acid repeat sequence that exhibits homology to a repeat sequence found in the largest subunit of RNA polymerase II. cypher1 and cypher2 mRNAs exhibited identical expression patterns. Both are exclusively expressed in cardiac and striated muscle in embryonic and adult stages. By biochemical assays, we have demonstrated that Cypher1 and Cypher2 bind to alpha-actinin-2 via their PDZ domains. This interaction has been further confirmed by immunohistochemical studies that demonstrated co-localization of Cypher and alpha-actinin at the Z-lines of cardiac muscle. We have also found that Cypher1 binds to protein kinase C through its LIM domains. Phosphorylation of Cypher by protein kinase C has demonstrated the functional significance of this interaction. Together, our data suggest that Cypher1 may function as an adaptor in striated muscle to couple protein kinase C-mediated signaling, via its LIM domains, to the cytoskeleton (alpha-actinin-2) through its PDZ domain.

Authors: Q Zhou, P Ruiz-Lozano, M E Martone, J Chen

Date Published: 3rd Jul 1999

Publication Type: Not specified

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