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Rho transcription inhibitor CCG-1423 effect on PC-3 cells

ABSTRACT: Analysis of serum starved PC-3 cells treated with CCG-1423, Latrunculin B, or the transcription elongation inhibitor DRB for 2 or 24 hours. Results provide insights to potential therapeutic approaches to cancer metastasis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE30188 | GEO | 2013/05/01

SECONDARY ACCESSION(S): PRJNA143975

REPOSITORIES: GEO

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Rho transcription inhibitor CCG-1423 effect on PC-3 cells

Project description:Analysis of serum starved PC-3 cells treated with CCG-1423, Latrunculin B, or the transcription elongation inhibitor DRB for 2 or 24 hours. Results provide insights to potential therapeutic approaches to cancer metastasis. Twenty one samples in triplicate were analyzed and compared to the DMSO-treated control. The primary condition tested was the effect of the Rho-transcription pathway inhibitor, CCG-1423 As a biologically related control, the actin polymerization inhibitor, Latrunculin B, that also blocks Rho-stimulated gene transcription was tested. As a control for non-specific transcription inhibition, DRB was used. All samples, 2-hr and 24-hr treated samples were compared to the 24-hr DMSO sample.

2013-05-01 | E-GEOD-30188 | biostudies-arrayexpress

CCG-1423-derived compounds reduce global RNA synthesis and inhibit transcriptional responses (PRO-seq)

Project description:Myocardin-related transcription factors (MRTFs) are coactivators of serum response factor (SRF), and thereby regulate cytoskeletal gene expression in response to actin dynamics. MRTFs have also been implicated in heat shock protein (hsp) transcription in fly ovaries, but the mechanisms remain unclear. Here we demonstrate that in mammalian cells, MRTFs are dispensable for hsp gene induction. However, the widely used small molecule inhibitors of MRTF/SRF transcription pathway, derived from CCG-1423, efficiently inhibit hsp gene transcription in both fly and mammalian cells also in absence of MRTFs. Quantifying RNA synthesis and RNA polymerase distribution demonstrates that CCG-1423-derived compounds have a genome-wide effect on transcription. Indeed, tracking nascent transcription at nucleotide resolution reveals that CCG-1423-derived compounds reduce RNA polymerase II elongation, and severely dampen the transcriptional response to heat shock. The effects of CCG-1423-derived compounds therefore extend beyond the MRTF/SRF pathway into nascent transcription, opening novel opportunities for their use in transcription research.

2023-10-03 | GSE244231 | GEO

CCG-1423-derived compounds reduce global RNA synthesis and inhibit transcriptional responses (ChIP-seq)

2023-09-26 | GSE243873 | GEO

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Project description:Rho transcription inhibitor CCG-1423 effect on PC-3 cells

| PRJNA143975 | ENA

CCg Progenitors

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2005-06-16 | GSE2499 | GEO

Targeting MRTF/SRF in CAP2-dependent dilated cardiomyopathy delays disease onset

Project description:About one third of dilated cardiomyopathy (DCM) cases are caused by mutations in sarcomere or cytoskeletal proteins. Yet treating the cytoskeleton directly is not possible because drugs that bind to actin are not well tolerated. Mutations in the actin binding protein CAP2 can cause DCM and knockout mice, either whole body (CAP2 KO) or cardiomyocyte specific knockouts (CAP2 CKO), develop DCM with cardiac conduction disease. RNA-seq analysis of CAP2 KO hearts and isolated cardiomyocytes revealed over-activation of fetal genes including serum response factor (SRF) regulated genes such as Myl9 and Acta2 prior to the emergence of cardiac disease. To test if we could treat CAP2 KO mice, we synthesized and tested the SRF inhibitor CCG-1423-8u. CCG-1423-8u reduced expression of the SRF targets Myl9 and Acta2, as well as the biomarker of heart failure, NPPA. The median survival of CAP2 CKO mice was 98 days, while CCG-1423-8u treated CKO mice survived for 116 days and also maintain normal cardiac function longer. These results suggest that some forms of sudden cardiac death and cardiac conduction disease are under cytoskeletal stress and that inhibiting signaling through SRF may benefit DCM by reducing cytoskeletal stress.

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CCG Multicentric Italian Lung Detection

Project description:CCG Multicentric Italian Lung Detection

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CCG Multicentric Italian Lung Detection

Project description:CCG Multicentric Italian Lung Detection

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RPEL proteins are the molecular targets for CCG-1423, an inhibitor of Rho signaling.

Project description: Not available

| S-EPMC3928398 | biostudies-literature

Impact of tRNA-Glu(UUC) and tRNA-Arg(CCG) on mRNA abundance

Project description:Stable expression of tRNA-Glu(UUC) and tRNA-Arg(CCG) followed by transcriptomic profiling to measure transcripts.