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Genes Targeted by the Hedgehog-Signaling Pathway can be Regulated by Estrogen Related Receptor β

ABSTRACT: We report Hedgehog signaling responsive genes with or without Esrrb in NI3T3 cells. Using Hh-responsive cells, we used RNA-Seq to find Hh responsive genes. In addition, we tested Esrrb's modification on Hh target genes' response.

ORGANISM(S): Mus musculus

PROVIDER: GSE71209 | GEO | 2015/11/06

SECONDARY ACCESSION(S): PRJNA290586

REPOSITORIES: GEO

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Genes Targeted by the Hedgehog-Signaling Pathway can be Regulated by Estrogen Related Receptor Î²

Project description:We report Hedgehog signaling responsive genes with or without Esrrb in NI3T3 cells. Using Hh-responsive cells, we used RNA-Seq to find Hh responsive genes. In addition, we tested Esrrb's modification on Hh target genes' response. Control vector transfected cells with vehicle treatment, Esrrb expression vector transfected cell with vehicle treatment, control vector transfected cells with Hh conditioned medium treatment, Esrrb expression vector transfected cell with Hh conditioned medium treatment,

2015-11-06 | E-GEOD-71209 | biostudies-arrayexpress

Sutherlanida extract inhibits Hedgehog signaling target genes

Project description:Sutherlandia frutescens (L) R. Br. (Sutherlandia) is a South African botanical that is traditionally used to treat a variety of health conditions, infections and diseases, including cancer. We hypothesized Sutherlandia might act through Gli/ Hedgehog (Hh)-signaling in prostate cancer cells and used RNA-Seq transcription profiling to profile gene expression in TRAMPC2 murine prostate cancer cells with or without Sutherlandia extracts. We found 50% of Hh-responsive genes can be repressed by Sutherlandia ethanol extract, including the canonical Hh-responsive genes Gli1 and Ptch1 as well as newly distinguished Hh-responsive genes Hsd11b1 and Penk.

2016-12-07 | GSE75760 | GEO

Transcription profiling of mouse E18.5 intestinal mesenchyme treated with Sonic or Indian hedgehog ligand to identify targets regulated by Hedgehog signaling

Project description:Epithelial Hedgehog (Hh) ligands regulate several aspects of fetal intestinal organogenesis and emerging data implicate the Hh pathway in inflammatory signaling in adult colon. We investigated the effects of chronic Hh inhibition in vivo and profiled molecular pathways acutely modulated by Hh signaling in the intestinal mesenchyme. Experiment Overall Design: E18.5 intestinal mesenchyme was isolated and cultured. Mesenchyme was treated with Sonic (Shh) or Indian (Ihh) hedgehog ligand or Vehicle (control) acutely to identify targets regulated by Hh signaling in intestinal mesenchyme.

2009-11-10 | E-GEOD-17840 | biostudies-arrayexpress

Targeted protein degradation reveals BET bromodomains as the cellular target of Hedgehog Pathway Inhibitor-1

Project description:Target deconvolution of small molecule hits from phenotypic screens presents a major challenge. Illustrative of these are the many screens that have been conducted to find inhibitors for the Hedgehog (Hh) signaling pathway – a major developmental pathway with many implications in health and disease - with many hits but very few identified cellular targets. We here present a strategy for target identification based on Proteolysis-Targeting Chimeras (PROTACs), combined with label-free quantitative proteomics. We developed a PROTAC based on the downstream Hedgehog Pathway Inhibitor-1 (HPI-1), a phenotypic screen hit with unknown cellular target. Using our Hedgehog Pathway PROTAC (HPP) we identified and validated BET bromodomains to be the cellular targets of HPI-1. Furthermore, we found that HPP-9 has a unique mechanism of action as a long-acting Hh pathway inhibitor through prolonged BET bromodomain degradation. Collectively, we provide a powerful PROTAC-based approach for target deconvolution, that has answered the longstanding question of the cellular target of HPI-1 and yielded the first PROTAC that acts on the Hh pathway.

2023-07-20 | PXD036539 | Pride

Targeted protein degradation reveals BET bromodomains as the cellular target of Hedgehog Pathway Inhibitor-1

2023-07-20 | PXD040859 | Pride

Targeted protein degradation reveals BET bromodomains as the cellular target of Hedgehog Pathway Inhibitor-1

2023-06-05 | GSE228015 | GEO

Smoothened Transduces Hedgehog Signals via Activity-Dependent Sequestration of PKA Subunits

Project description:The Hedgehog (Hh) pathway is essential for tissue homeostasis, and misregulation of this cascade drives several cancers. To control expression of pathway target genes, the G protein-coupled receptor (GPCR) Smoothened (SMO) activates glioma-associated (GLI) transcription factors via an unknown mechanism. Here we show that, rather than conforming to traditional GPCR signaling paradigms, SMO activates GLI by binding and sequestering protein kinase A (PKA) catalytic subunits at the membrane. This sequestration, triggered by GPCR kinase 2 (GRK2)-mediated phosphorylation of SMO intracellular domains, prevents PKA from phosphorylating soluble substrates, releasing GLI from PKA-mediated inhibition. Our work provides a mechanism directly linking vertebrate Hh signal transduction at the membrane to transcription factor activation in the nucleus. In contrast to existing models, our work shows that this aspect of Hh signaling is fundamentally similar between species. The mechanism described here may apply broadly to other GPCR- and PKA-containing cascades.

2021-04-25 | PXD019346 | Pride

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2021-07-08 | GSE171689 | GEO