Similar Datasets
Project description:Poor skeletal muscle fitness contributes to many chronic disease states including obesity, heart failure, primary muscle disorders, and age-related sarcopenia. Receptor Interacting Protein 140 (RIP140) is a striated muscle-enriched nuclear receptor co-regulator. To investigate the role of RIP140 in skeletal muscle, striated muscle-specific RIP140-deficient (strNrip1-/-) mice were generated and characterized. strNrip1-/- mice display a remarkable endurance performance phenotype based on endurance treadmill performance, VO2max testing, and functional assessment of isolated muscle. RNA-sequence analysis of glycolytic fast-twitch muscle from the strNrip1-/- mice identified a broad array of differentially upregulated metabolic and structural muscle genes involved in muscle endurance fitness pathways including mitochondrial biogenesis and respiration, fatty acid oxidation, triglyceride dynamics, muscle fiber type, angiogenesis, and neuromuscular junction (NMJ) remodeling. Assessment of the structural correlates of these processes confirmed the function of RIP140 as placing a “brake” on the transcriptional network controlling these key muscle endurance fitness processes. Integration of the RNA sequence results with CUT&RUN analysis of strNrip1-/- myotubes identified direct RIP140 targets including genes involved in fatty acid metabolism and NMJ biogenesis. We conclude that RIP140 serves as a physiological “rheostat” for a broad network of genes involved in skeletal muscle fitness.
2025-08-27 | GSE289567 | GEO
Project description:Poor skeletal muscle fitness contributes to many chronic disease states including obesity, heart failure, primary muscle disorders, and age-related sarcopenia. Receptor Interacting Protein 140 (RIP140) is a striated muscle-enriched nuclear receptor co-regulator. To investigate the role of RIP140 in skeletal muscle, striated muscle-specific RIP140-deficient (strNrip1-/-) mice were generated and characterized. strNrip1-/- mice display a remarkable endurance performance phenotype based on endurance treadmill performance, VO2max testing, and functional assessment of isolated muscle. RNA-sequence analysis of glycolytic fast-twitch muscle from the strNrip1-/- mice identified a broad array of differentially upregulated metabolic and structural muscle genes involved in muscle endurance fitness pathways including mitochondrial biogenesis and respiration, fatty acid oxidation, triglyceride dynamics, muscle fiber type, angiogenesis, and neuromuscular junction (NMJ) remodeling. Assessment of the structural correlates of these processes confirmed the function of RIP140 as placing a “brake” on the transcriptional network controlling these key muscle endurance fitness processes. Integration of the RNA sequence results with CUT&RUN analysis of strNrip1-/- myotubes identified direct RIP140 targets including genes involved in fatty acid metabolism and NMJ biogenesis. We conclude that RIP140 serves as a physiological “rheostat” for a broad network of genes involved in skeletal muscle fitness.
2025-08-27 | GSE289576 | GEO
Project description:Poor skeletal muscle fitness contributes to many chronic disease states including obesity, heart failure, primary muscle disorders, and age-related sarcopenia. Receptor Interacting Protein 140 (RIP140) is a striated muscle-enriched nuclear receptor co-regulator. To investigate the role of RIP140 in skeletal muscle, striated muscle-specific RIP140-deficient (strNrip1-/-) mice were generated and characterized. strNrip1-/- mice display a remarkable endurance performance phenotype based on endurance treadmill performance, VO2max testing, and functional assessment of isolated muscle. RNA-sequence analysis of glycolytic fast-twitch muscle from the strNrip1-/- mice identified a broad array of differentially upregulated metabolic and structural muscle genes involved in muscle endurance fitness pathways including mitochondrial biogenesis and respiration, fatty acid oxidation, triglyceride dynamics, muscle fiber type, angiogenesis, and neuromuscular junction (NMJ) remodeling. Assessment of the structural correlates of these processes confirmed the function of RIP140 as placing a “brake” on the transcriptional network controlling these key muscle endurance fitness processes. Integration of the RNA sequence results with CUT&RUN analysis of strNrip1-/- myotubes identified direct RIP140 targets including genes involved in fatty acid metabolism and NMJ biogenesis. We conclude that RIP140 serves as a physiological “rheostat” for a broad network of genes involved in skeletal muscle fitness.
2025-08-27 | GSE289569 | GEO
Project description:A Role for the Transcriptional Coregulator RIP140 in the Control of Muscle Endurance Fitness
| PRJNA1223455 | ENA
Project description:A Role for the Transcriptional Coregulator RIP140 in the Control of Muscle Endurance Fitness [CUTnRUN_Ac_flat]
| PRJNA1223459 | ENA
Project description:A Role for the Transcriptional Coregulator RIP140 in the Control of Muscle Endurance Fitness [RNASeq_Training_strKO_flat]
| PRJNA1223460 | ENA
Project description:A Role for the Transcriptional Coregulator RIP140 in the Control of Muscle Endurance Fitness [RNASeq_MyogeninCre_flat]
| PRJNA1223461 | ENA
Project description:PurposeReceptor-interacting protein of 140 kDa (RIP140) is a transcriptional cofactor for nuclear receptors involved in reproduction and energy homeostasis. Our aim was to investigate its role in the regulation of E2F1 activity and target genes both in breast cancer cell lines and in tumor biopsies.Experimental designGlutathione S-transferase pull-down assays, coimmunoprecipitation experiments, and chromatin immunoprecipitation analysis were used to evidence interaction between RIP140 and E2F1. The effects of RIP140 expression on E2F1 activity were determined using transient transfection and quantification of E2F target mRNAs by quantitative real-time PCR. The effect on cell cycle was assessed by fluorescence-activated cell sorting analysis on cells overexpressing green fluorescent protein-tagged RIP140. A tumor microarray data set was used to investigate the expression of RIP140 and E2F1 target genes in 170 breast cancer patients.ResultsWe first evidenced the complex interaction between RIP140 and E2F1 and showed that RIP140 represses E2F1 transactivation on various transiently transfected E2F target promoters and inhibits the expression of several E2F1 target genes (such as CCNE1 and CCNB2). In agreement with a role for RIP140 in the control of E2F activity, we show that increasing RIP140 levels results in a reduction in the proportion of cells in S phase in various human cell lines. Finally, analysis of human breast cancers shows that low RIP140 mRNA expression was associated with high E2F1 target gene levels and basal-like tumors.ConclusionThis study shows that RIP140 is a regulator of the E2F pathway, which discriminates luminal- and basal-like tumors, emphasizing the importance of these regulations for a clinical cancer phenotype.
| S-EPMC3112174 | biostudies-literature
Project description:Colon cancer frequently results from mutations that constitutively activate the Wnt signaling pathway, a major target being the tumor suppressor gene adenomatous polyposis coli (APC). We recently identified the transcription factor RIP140 as a new inducer of APC gene transcription that inhibits colon cancer cell growth and impedes the Wnt signaling pathway by reducing β-catenin activation.
| S-EPMC4905177 | biostudies-other
Project description:Circadian rhythms are generated in central and peripheral tissues by an intracellular oscillating timing mechanism known as the circadian clock. Several lines of evidence show a strong and bidirectional interplay between metabolism and circadian rhythms. Receptor interacting protein 140 (RIP140) is a coregulator for nuclear receptors and other transcription factors that represses catabolic pathways in metabolic tissues. Although RIP140 functions as a corepressor for most nuclear receptors, mounting evidence points to RIP140 as a dual coregulator that can repress or activate different sets of genes. Here, we demonstrate that RIP140 mRNA and protein levels are under circadian regulation and identify RIP140 as a modulator of clock gene expression, suggesting that RIP140 can participate in a feedback mechanism affecting the circadian clock. We show that the absence of RIP140 disturbs the basal levels of BMAL1 and other clock genes, reducing the amplitude of their oscillations. In addition, we demonstrate that RIP140 is recruited to retinoid-related orphan receptor (ROR) binding sites on the BMAL1 promoter, directly interacts with RORα, and increases transcription from the BMAL1 promoter in a RORα-dependent manner. These results indicate that RIP140 is not only involved in metabolic control but also acts as a coactivator for RORα, influencing clock gene expression.
| S-EPMC3207295 | biostudies-literature