Saccharomyces cerevisiae
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA318254 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3362690_1.fastq.gz | Fastqsanger.gz | |||
| SRR3362690_2.fastq.gz | Fastqsanger.gz | |||
| SRR3362700_1.fastq.gz | Fastqsanger.gz | |||
| SRR3362700_2.fastq.gz | Fastqsanger.gz | |||
| SRR3362681_1.fastq.gz | Fastqsanger.gz |
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Project description:In the related work, proteins were computationally designed and experimentally optimized to bind with high affinity and specificity to each human pro-survival BCL2 homolog. Site-directed saturation mutagenesis libraries were generated based on partially-specific computational designs 2CDP06 (for Bcl-2-targeting Computationally Designed Protein), XCDP07 (Bcl-xL), WCDP03 (Bcl-w), and FCDP01 (Bfl-1), and BCDP01 (Bcl-B) which were then transformed into yeast for surface display, as described in Chao et al (Nat Protoc. 2006). Binding to labeled target homolog was detected via FACS after co-incubation with unlabeled competitors to favor specific interactions. Similarly, an SSM library was generated based on partially-specific Mcl-1-targeting design MCDP02 and was sorted for specific interactions toward each Bcl-2 proteins (data labeled MCDP02_[homolog]). DNA was harvested from naïve libraries and sorted populations and deep sequenced. The frequency of each mutation in a sorted population was compared to its frequency in the naïve population to determine enrichment ratios for all possible single amino acid substitutions (frequency calculations based on counts, which can be found in analyzed data file along with enrichment ratios). The most enriching mutations were then combined in combinatorial libraries, sorted as described above, and variants present after four or five rounds of sorting exhibited excellent specificity. Please see our corresponding publication for additional detail.
2016-05-09 | GSE80194 | GEO
Project description:Experimental evolution of BCL2 family ancestral proteins
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Project description:A systems approach to delineate functions of YAP family members
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Project description:Overexpression of antiapoptotic BCL2 family proteins occurs in various hematologic malignanices and contributes to leukemogenesis by inhibiting the apoptotic machinery of the cells. BH3 mimetics provide an option for medication, with venetoclax as the first drug applied for chronic lymphocytic leukemia and for acute myeloid leukemia. To find additional hematologic entities with ectopic expression of BCL2 family members, we performed expression screening applying the LL-100 panel. Primary effusion lymphoma (PEL) and anaplastic large cell lymphoma (ALCL), 2/22 entities covered by this panel, stood out by high expression of MCL1 and low expression of BCL2. The MCL1 inhibitor AZD-5991 induced apoptosis in both malignancies suggesting that this BH3 mimetic might be efficient as drug for these diseases. The ALCL cell lines also expressed BCLXL and BCL2A1, both contributing to survival of the cells. The combination of specific BH3 mimetics yielded synergistic effects, pointing to a novel strategy for the treatment of ALCL. The PI3K/AKT inhibitor BEZ-235 could also efficiently be applied in combination with AZD-5991, providing an alternative to avoid thrombocytothemia, which is associated with the use of BCLXL inhibitors.
2021-12-31 | E-MTAB-10903 | biostudies-arrayexpress
Project description:The translocation t(14;18) activates BCL2 and is considered the initiating genetic lesion in most follicular lymphomas (FL). Surprisingly, FL patients fail to respond to the BCL2 inhibitor, Venetoclax. We show that mutations and deletions affecting the histone lysine methyltransferase SETD1B (KMT2G) occur in 7% of FLs and in 16% of diffuse large B cell lymphomas (DLBCL). Deficiency in SETD1B confers striking resistance to Venetoclaxand to an experimental MCL-1 inhibitor. SETD1B also acts as a tumor suppressor andcooperates with loss ofKMT2Din lymphoma development in vivo. Consistently, loss of SETD1B in human lymphomas typically coincides with loss of KMT2D. Mechanistically, SETD1B is required for the expression of several pro-apoptotic BCL2 family proteins. Conversely, inhibitors of the KDM5 histoneH3K4demethylases restore BIM and BIK expression and synergize with Venetoclax inSETD1B-deficient lymphomas.
2024-08-23 | GSE273154 | GEO
Project description:The translocation t(14;18) activates BCL2 and is considered the initiating genetic lesion in most follicular lymphomas (FL). Surprisingly, FL patients fail to respond to the BCL2 inhibitor, Venetoclax. We show that mutations and deletions affecting the histone lysine methyltransferase SETD1B (KMT2G) occur in 7% of FLs and in 16% of diffuse large B cell lymphomas (DLBCL). Deficiency in SETD1B confers striking resistance to Venetoclaxand to an experimental MCL-1 inhibitor. SETD1B also acts as a tumor suppressor andcooperates with loss ofKMT2Din lymphoma development in vivo. Consistently, loss of SETD1B in human lymphomas typically coincides with loss of KMT2D. Mechanistically, SETD1B is required for the expression of several pro-apoptotic BCL2 family proteins. Conversely, inhibitors of the KDM5 histoneH3K4demethylases restore BIM and BIK expression and synergize with Venetoclax inSETD1B-deficient lymphomas.
2024-08-23 | GSE273153 | GEO
Project description:The translocation t(14;18) activates BCL2 and is considered the initiating genetic lesion in most follicular lymphomas (FL). Surprisingly, FL patients fail to respond to the BCL2 inhibitor, Venetoclax. We show that mutations and deletions affecting the histone lysine methyltransferase SETD1B (KMT2G) occur in 7% of FLs and in 16% of diffuse large B cell lymphomas (DLBCL). Deficiency in SETD1B confers striking resistance to Venetoclaxand to an experimental MCL-1 inhibitor. SETD1B also acts as a tumor suppressor andcooperates with loss ofKMT2Din lymphoma development in vivo. Consistently, loss of SETD1B in human lymphomas typically coincides with loss of KMT2D. Mechanistically, SETD1B is required for the expression of several pro-apoptotic BCL2 family proteins. Conversely, inhibitors of the KDM5 histoneH3K4demethylases restore BIM and BIK expression and synergize with Venetoclax inSETD1B-deficient lymphomas.
2024-08-23 | GSE273152 | GEO
Project description:Activation of the MYC oncogene is common in B-cell lymphomas, and frequently associated with compensatory events that dampen Myc-induced apoptosis, such as over-expression of anti-apoptotic Bcl2-family proteins. For example, concurrent translocations of MYC and BCL2 in a subset of Diffuse large B-cell lymphoma (DLBCL) lead to the high-grade “double-hit” lymphoma subtype (DHL), characterized by dismal prognosis in the face of current front-line regimens, thus calling for the pursuit of tailored therapeutic strategies. Here, we show that Myc and Bcl2 modulate the sensitivity of B-cells to IACS-010759, a selective inhibitor of mitochondrial respiratory complex I. Myc activation in non-transformed lymphoid precursors suppressed endogenous Bcl2 and sensitized the cells to IACS-010759-induced apoptosis. Treatment with the Bcl2 inhibitor venetoclax also sensitized to IACS-010759, while overexpression of Bcl-2 was protective. IACS-010759 engaged an ATF4-driven Integrated Stress Response (ISR) with dual anti- and pro-apoptotic effects, the latter mediated by the CHOP transcription factor, which contributed to selective killing of Myc-overexpressing cells. In line with the above data, IACS-010759 and venetoclax synergized in killing human DHL cells, and showed strong combinatorial effects in a pre-clinical setting. In a Bcl2-negative Burkitt’s lymphoma cell line, instead, IACS-010759 synergized with the Mcl-1 inhibitor S63845. Altogether, our data point to the combination of IACS-010759 with distinct Bcl2-family inhibitors for therapeutic reactivation of the intrinsic apoptotic pathway in Myc-associated B-cell lymphomas
2022-03-01 | GSE149073 | GEO
Project description:Raw MS files accompanying manuscript Jason Z Zhang et. al. "Computationally designed sensors detect Ras activity and signaling effectors at subcellular resolution." (2023)
2023-11-24 | MSV000093478 | MassIVE