Similar Datasets
Project description:This study investigated the transcriptional impact of hypomorphic bcl-11 mutations.
2025-12-10 | GSE293058 | GEO
Project description:BCL-11 enables adaptive stress responses to environmental challenges
| PRJNA1242846 | ENA
Project description:BCL-11 enables adaptive stress responses to environmental challenges
| PRJNA1242710 | ENA
Project description:Background: We hypothesized that spleen microarray gene expression profiles analyzed with contemporary pathway analysis software would provide molecular pathways of interest and target genes that might help explain the affect of bcl-2 on improving survival during sepsis. Methods: Two mouse models of sepsis, cecal ligation and puncture and tracheal instillation of Pseudomonas aeruginosa, were tested in both wild-type mice and mice that overexpress bcl-2. Whole spleens were obtained 6 hours after septic injury. DNA microarray transcriptional profiles were obtained using the Affymetrix 430A GeneChip, containing 22,690 elements. Ingenuity Pathway Analysis software was used to construct hypothetical transcriptional networks that changed in response to sepsis and expression of the bcl-2 transgene. Results: A conservative approach was used wherein only changes induced by both abdominal and pulmonary sepsis were studied. At 6 hours, sepsis induced alterations in the abundance of hundreds of spleen genes, including a number of proinflammatory mediators (e.g., IL-6). These sepsis-induced alterations were blocked by expression of the bcl-2 transgene. Network analysis implicated a number of bcl-2-related apoptosis genes, including bcl2L11 (bim), bcl-2L2 (bcl-w), bmf, and mcl-1. Sepsis in bcl-2 transgenic animals resulted in alteration of RNA abundance for only a single gene, ceacam1. Conclusion: These findings are consistent with sepsis-induced alterations in the balance of pro- and anti-apoptotic transcriptional networks. In addition, our data suggest that the ability of bcl-2 overexpression to improve survival in sepsis in this model is related in part to prevention of sepsis-induced alterations in spleen transcriptional responses. Keywords: Sepsis, bcl-2, wildtype, spleen, RNA expression, microarray
2007-02-15 | GSE5811 | GEO
Project description:Overexpression of BCL-xL and BCL-2 play key roles in tumorigenesis and cancer drug resistance. Advances in PROTAC technology facilitated recent development of the first BCL-xL/BCL-2 dual degrader, 753b, a VHL-based degrader with improved potency and reduced toxicity compared to previous small molecule inhibitors. Here, we determined crystal structures of VHL/753b/BCL-xL and VHL/753b/ BCL-2 ternary complexes. The two ternary complexes exhibit markedly different architectures that are accompanied by distinct networks of interactions at the VHL/PZ753b-linker/target interfaces. The importance of these interfacial contacts was validated via functional analysis and informed subsequent rational and structure-guided design focused on the 753b linker and BCL-2/BCL-xL warhead. This resulted in the design of a novel degrader, WH244, with enhanced potency to degrade BCL-xL/BCL-2 in cells. Using biophysical assays followed by in cell activities, we were able to explain the enhanced target degradation of BCL-2/BCL-xL in cells. Most PROTACs are empirically designed and lack structural studies, making it challenging to understand their modes of action and specificity. Our work presents a streamlined approach that combines rational design and structure-based insights backed with cell-based studies to develop effective PROTAC-based cancer therapeutics.
2024-03-12 | PXD049976 | Pride
Project description:The anti-apoptotic function of Bcl-xL in the heart against reperfusion injury is diminished by K-Ras-Mst1-mediated phosphorylation of Ser14, which allows dissociation of Bcl-xL from Bax and promotes cardiomyocyte death. Here we show that Ser14 phosphorylation of Bcl-xL is also promoted by hemodynamic stress in the heart, through the H-Ras-ERK pathway. Our study suggests that phosphorylation of Bcl-xL at Ser14 in response to acute pressure overload plays an essential role in mediating compensatory hypertrophy by promoting calcium release, alleviating the negative constraint of Bcl-xL upon the IP3R-NFAT pathway.
2023-09-06 | PXD045118 | Pride
Project description:Overexpression of BCL-xL and BCL-2 play key roles in tumorigenesis and cancer drug resistance. Advances in PROTAC technology facilitated recent development of the first BCL-xL/BCL-2 dual degrader, 753b, a VHL-based degrader with improved potency and reduced toxicity compared to previous small molecule inhibitors. Here, we determined crystal structures of VHL/753b/BCL-xL and VHL/753b/ BCL-2 ternary complexes. The two ternary complexes exhibit markedly different architectures that are accompanied by distinct networks of interactions at the VHL/PZ753b-linker/target interfaces. The importance of these interfacial contacts was validated via functional analysis and informed subsequent rational and structure-guided design focused on the 753b linker and BCL-2/BCL-xL warhead. This resulted in the design of a novel degrader, WH244, with enhanced potency to degrade BCL-xL/BCL-2 in cells. Using biophysical assays followed by in cell activities, we were able to explain the enhanced target degradation of BCL-2/BCL-xL in cells. Most PROTACs are empirically designed and lack structural studies, making it challenging to understand their modes of action and specificity. Our work presents a streamlined approach that combines rational design and structure-based insights backed with cell-based studies to develop effective PROTAC-based cancer therapeutics.
2024-02-21 | MSV000094144 | MassIVE
Project description:Bcl-2 is highly enriched in the nervous system during neural development and plays an important role in modulating cell survival. In addition to its anti-apoptotic function, Bcl-2 has previously been suggested as a mediator of neuronal differentiation. However, the mechanism by which Bcl-2 might influence neurogenesis is not sufficiently understood. We aimed to determine the non-apoptotic functions of Bcl-2 during neuronal differentiation.
2019-05-01 | GSE130481 | GEO
Project description:miRNAs profiling of HepG2 cells comparing vector-control treated HepG2 cells with HepG2 cells transfected with Twist1, Bcl-2, and Twist1/Bcl-2 plasmids. Microarray analysis revealed a panel of miRNAs with significant differential expression among these four HCC cell lines.
2017-02-10 | GSE77501 | GEO
Project description:Bacillus siamensis strain:BCL Genome sequencing and assembly
| PRJNA1022477 | ENA