Saccharomyces cerevisiae
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA396954 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The conserved Ccr4-Not complex regulates all aspects of the RNA polymerase II (Pol II) gene expression pathway, while it also controls proteasome assembly and function. The Not4 RING domain ubiquitin ligase is a core subunit that also contains an RNA recognition motif (RRM) and C3H1 domain (collectively referred to as the RRM-C) whose function is unknown. Herein, we demonstrate that the Not4 RRM-C contributes to both Not4-dependent regulation of the proteasome and Pol II. Disruption of both Not4 ligase activity and the RRM-C domain simultaneously replicates the proteasome-dependent deubiquitylation and catalytic activity misregulation found in Not4-deficient cells. Transcriptome analysis reveals that the Not4 RRM-C affects a subset of Pol II-dependent genes involved in specific biological functions, including transcription elongation, cyclin-dependent kinase regulated nutrient responses, and ribosomal biogenesis. At these genes, the Not4 RRM-C negatively regulates Pol II binding. While Not4 RRM-C disruption modestly increases between Ccr4-Not and Pol II, a Not4 ligase mutant decreases Ccr4-Not association with Pol II, thus implicating Not4-dependent ubiquitylation in mediating Ccr4-Not interaction with Pol II. Collectively, our results suggests the cellular RNA environment may integrate control of global proteostasis and Pol II transcription through the Not4 ubiquitin ligase.
2017-08-03 | GSE102192 | GEO
Project description:Dosage compensation in Drosophila is an epigenetic phenomenon utilizing proteins and long non-coding RNAs (lncRNAs) for transcriptional up-regulation of the entire X-chromosome. Here, UV cross-linking followed by deep sequencing (iCLIP) show that two enzymes in the Male-Specific Lethal complex, MLE RNA helicase and MSL2 ubiquitin ligase, bind evolutionarily conserved domains containing tandem stem-loops in roX1 and roX2 RNAs in vivo.
2013-07-18 | E-MTAB-1669 | biostudies-arrayexpress
Project description:Analysis of E14 embryonic stem cells lacking Trip12 ubiquitin ligase activity. We used microarrays to detail the global gene expression profiles affected by Trip12 ubiquitin ligase activity in mouse embryonic stem cell. Total RNA was extracted from wild-type and Trip12 mutant mouse embryonic stem cells and hybridized on Affymetrix microarrays.
2014-01-01 | E-GEOD-27527 | biostudies-arrayexpress
Project description:Nuclear hormone receptors (NRs) are ligand-binding transcription factors that are widely targeted therapeutically. Hormone binding triggers NR activation and their subsequent proteasomal degradation through unknown ligand-dependent ubiquitin ligase machinery. NR degradation is therapeutically relevant. Efficacy of all-trans-retinoic acid (ATRA) for the treatment of acute promyelocytic leukemia requires degradation of the oncogenic fusion between the Promyelocytic Leukemia Protein (PML) with the Retinoic Acid Receptor Alpha (RARA). Here we use CRISPR-based screens to identify the HECT E3 ubiquitin ligase UBR5 as a ligase for PML-RARA and RARA and observe an agonist-dependent association between RARA and UBR5, which occurs directly on chromatin to regulate transcription. We present the cryo-EM structure of full-length human UBR5 and identify a Leu-X-X-Leu-Leu (LxxLL) binding motif that associates with a conserved degron in RARA. A high-resolution crystal structure of the RARA ligand binding domain in complex with this LxxLL motif shows how UBR5 binding is mutually exclusive with nuclear co-activator engagement. We demonstrate that UBR5 utilizes this conserved degron to additionally regulate hormone dependent protein stability for the glucocorticoid, progesterone, and vitamin D receptors. Our work establishes UBR5-driven NR degradation as an integral regulator of transcriptional signaling by nuclear hormones.
2023-07-20 | PXD041749 | Pride
Project description:Nuclear hormone receptors (NRs) are ligand-binding transcription factors that are widely targeted therapeutically. Hormone binding triggers NR activation and their subsequent proteasomal degradation through unknown ligand-dependent ubiquitin ligase machinery. NR degradation is therapeutically relevant. Efficacy of all-trans-retinoic acid (ATRA) for the treatment of acute promyelocytic leukemia requires degradation of the oncogenic fusion between the Promyelocytic Leukemia Protein (PML) with the Retinoic Acid Receptor Alpha (RARA). Here we use CRISPR-based screens to identify the HECT E3 ubiquitin ligase UBR5 as a ligase for PML-RARA and RARA and observe an agonist-dependent association between RARA and UBR5, which occurs directly on chromatin to regulate transcription. We present the cryo-EM structure of full-length human UBR5 and identify a Leu-X-X-Leu-Leu (LxxLL) binding motif that associates with a conserved degron in RARA. A high-resolution crystal structure of the RARA ligand binding domain in complex with this LxxLL motif shows how UBR5 binding is mutually exclusive with nuclear co-activator engagement. We demonstrate that UBR5 utilizes this conserved degron to additionally regulate hormone dependent protein stability for the glucocorticoid, progesterone, and vitamin D receptors. Our work establishes UBR5-driven NR degradation as an integral regulator of transcriptional signaling by nuclear hormones.
2023-07-20 | PXD040953 | Pride
Project description:Analysis of E14 embryonic stem cells lacking Trip12 ubiquitin ligase activity. We used microarrays to detail the global gene expression profiles affected by Trip12 ubiquitin ligase activity in mouse embryonic stem cell.
2014-01-01 | GSE27527 | GEO
Project description:San1 is an E3 ubiquitin ligase involved in nuclear protein quality control via its interaction with intrinsically disordered proteins for ubiquitylation and 26S proteasomal degradation. Since a number of transcription/chromatin regulatory factors contain intrinsically disordered domains and can be inhibitory to transcription when in excess, San1 might be involved in regulation of transcription. To address this, we carried out ChIP-seq (Chromatin immunoprecipitation sequencing) here to analyze the role of San1 in genome-wide association of TBP (TATA-box binding protein that nucleates the preinitiation complex formation at the promoter for transcription initiation) and RNA polymerase II (that is recruited to the promoter by TBP and subsequently engaged in transcription elongation at the coding sequence for mRNA biosynthesis). Our results reveal the genome-wide role of San1 in facilitating the recruitment of TBP to the promoter, thus indicating its involvement in promoting the preinitiation complex formation for transcription initiation. Further, we find the global role of San1 in regulating RNA polymerase II at the coding sequence.
2021-12-04 | GSE190065 | GEO
Project description:Constitutively active androgen receptor (AR) signaling confers resistance to AR-targeted therapies. Here we show that the ubiquitin-mediated proteolysis pathway plays a critical role in the degradation of AR and its variants, particularly variant 7 (AR-V7). AR/AR-V7 proteinhomeostasis (proteostasis) requires interaction of the E3 ubiquitin ligase STUB1 and HSP70complex. STUB1 disassociates AR/AR-V7 from HSP70, leading to AR/AR-V7 ubiquitination and degradation. Inhibition of HSP70 reduces AR/AR-V7 expression which significantly inhibits prostate tumor growth and improves enzalutamide/abiraterone treatments. Clinically, HSP70 expression is upregulated and correlated with AR/AR-V7 levels in high Gleason scores prostate tumors. Our results reveal a novel mechanism of AR-V7 modulation via proteostasis which could be targeted to reduce AR-V7 expression and overcome resistance to AR-targeted therapies.
2018-10-05 | GSE120005 | GEO
Project description:Constitutively active androgen receptor (AR) signaling confers resistance to AR-targeted therapies. Here we show that the ubiquitin-mediated proteolysis pathway plays a critical role in the degradation of AR and its variants, particularly variant 7 (AR-V7). AR/AR-V7 proteinhomeostasis (proteostasis) requires interaction of the E3 ubiquitin ligase STUB1 and HSP70complex. STUB1 disassociates AR/AR-V7 from HSP70, leading to AR/AR-V7 ubiquitination and degradation. Inhibition of HSP70 reduces AR/AR-V7 expression which significantly inhibits prostate tumor growth and improves enzalutamide/abiraterone treatments. Clinically, HSP70 expression is upregulated and correlated with AR/AR-V7 levels in high Gleason scores prostate tumors. Our results reveal a novel mechanism of AR-V7 modulation via proteostasis which could be targeted to reduce AR-V7 expression and overcome resistance to AR-targeted therapies.
2018-10-05 | GSE120004 | GEO
Project description:The Illumina GoldenGate Genotyping Assay is a flexible, pre-optimized assay that uses a discriminatory DNA polymerase and ligase to interrogate 96 SNP loci simultaneously. This Assay utilizes the BeadArray Reader. Using this assay, we examined the distribution of the patients` genotypes to determine which genotype tends to have a better outcomes for cancer treatment.
2015-05-30 | GSE52072 | GEO