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Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress [ChIP-seq]

ABSTRACT: Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress [ChIP-seq]

PROVIDER: PRJNA913932 | ENA |

REPOSITORIES: ENA

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Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress [ChIP-seq]

Project description:Activated Notch signaling is highly prevalent in T-cell acute lymphoblastic leukemia (T-ALL). But in clinical trials, pan-Notch inhibitors caused excessive toxicity. To find alternative ways to target Notch signals, we investigated Cell division cycle 73 (Cdc73), which is a component of the RNA polymerase-associated transcriptional machinery and has been previously described as a Notch cofactor. Emerging evidence also suggests that transcriptional machinery might be an attractive vulnerability in T-ALL. In this setting, we show that CDC73 co-binds a subset of Notch-occupied regulatory elements in an ETS1-dependent context. In mouse models, Cdc73 is important for Notch-induced T-cell development and maintenance of Notch-induced T-ALL. Mechanistically, Cdc73, Ets1, and Notch activate genes that promote DNA repair and oxidative phosphorylation. Cdc73 induces these pathways through canonical functions in mRNA synthesis rather than non-canonical functions in enhancer activation. Our study suggests that Cdc73 acts through context-dependent mechanisms to promote a gene expression program that mitigates the genotoxic and metabolic stress of supraphysiological Notch signaling. We also provide mechanistic support for testing inhibitors of DNA repair, oxidative phosphorylation, and transcriptional machinery as anti-leukemic therapy while highlighting strategies that disable pathways that intersect with Notch at chromatin to target Notch signals without directly targeting the Notch complex.

2023-08-30 | GSE221339 | GEO

Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress [Bru-seq and BruUV-seq]

2023-08-30 | GSE219097 | GEO

Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress

Project description:Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress

| PRJNA913927 | ENA

Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress [Bru-seq and BruUV-seq]

Project description:Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress [Bru-seq and BruUV-seq]

| PRJNA907026 | ENA

Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-08-29 | GSE221345 | GEO

ROSALIND protects the mitochondrial translational machinery from oxidative damage

Project description:ROSALIND protects the mitochondrial translational machinery from oxidative damage

| PRJNA1049779 | ENA

Expression analysis of zebrafish TIF1g-deficient, cdc73 deficient and double-deficient embryos

Project description:Investigation of whole genome gene expression level changes in zebrafish TIF1g-deficient, cdc73 deficient and double-deficient embryos, compared to the wild-type ebryos. A twelve-chip study using total RNA isolated from gata1-GFP positive cells (sorted by FACS) from 12 somite-stage wild type embryos, TIF1g morholino injected, Cdc73 morpholino injected and double morpholino injected embryos.

2010-07-13 | E-GEOD-20432 | biostudies-arrayexpress

Mouse CDC73 AP-MS in AML - PAF1 complex interactions with SETDB1 mediate promoter H3K9 methylation and transcriptional repression of Hoxa9 and Meis1 in acute myeloid leukemia

Project description:Here we performed AP-MS experiments to find novel binding partners of CDC73 in mouse M1 AML cells. We also utilized a CDC73 mutant that does not support AML cell growth to determine functional consequences of gainin/ losing protein-protein interactions on mutation of this protein.

2018-05-22 | PXD009439 | Pride

TIF1g and cdc73 ChIP-chip data from K562 cells

Project description:We performed small-scale ChIP-chip (chrom 3,21, 22, X and Y) to reveal target locus of TIF1g and cdc73.

2010-08-02 | GSE20428 | GEO

RNA-seq for UBR5 and Cdc73-regulated genes in 4T1 cells treated with Dovitinib

Project description:In order to understand the molecular mechanisms underlying the regulatory activities of UBR5 and CDC73 in dovitinib-induced apoptosis in 4T1 tumor cells that were Dox-silenced for the expression of Ubr5, Cdc73, or both and treated with dovitinib.

2023-01-27 | GSE222787 | GEO

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