Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A genome-wide CRISPR/Cas9 screen in acute myeloid leukemia cells identifies regulators of TAK-243 sensitivity

ABSTRACT: A genome-wide CRISPR/Cas9 screen in acute myeloid leukemia cells identifies regulators of TAK-243 sensitivity

PROVIDER: PRJNA691473 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR13415206.fastq.gz	Fastqsanger.gz
	SRR13415207.fastq.gz	Fastqsanger.gz
	SRR13415208.fastq.gz	Fastqsanger.gz
	SRR13415209.fastq.gz	Fastqsanger.gz
	SRR13415210.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 18

Similar Datasets

A genome-wide CRISPR/Cas9 screen in acute myeloid leukemia cells identifies regulators of TAK-243 sensitivity

Project description:TAK-243 is a first-in-class inhibitor of ubiquitin-like modifier activating enzyme 1 (UBA1) that catalyzes ubiquitin activation, the first step in the ubiquitylation cascade. Based on its preclinical efficacy and tolerability, TAK-243 has been advanced to phase 1 clinical trials in advanced malignancies. Nonetheless, the determinants of TAK-243 sensitivity remain largely unknown. Here, we conducted a genome-wide CRISPR/Cas9 knockout screen in acute myeloid leukemia (AML) cells in the presence of TAK-243 to identify genes essential for TAK-243 action. We identified BEN domain-containing protein 3 (BEND3), a transcriptional repressor and a regulator of chromatin organization, as the top gene whose knockout confers resistance to TAK-243

2021-01-13 | GSE164639 | GEO

A genome-wide CRISPR/Cas9 screen in acute myeloid leukemia cells identifies regulators of TAK-243 sensitivity.

Project description:TAK-243 is a first-in-class inhibitor of ubiquitin-like modifier activating enzyme 1 that catalyzes ubiquitin activation, the first step in the ubiquitylation cascade. Based on its preclinical efficacy and tolerability, TAK-243 has been advanced to phase I clinical trials in advanced malignancies. Nonetheless, the determinants of TAK-243 sensitivity remain largely unknown. Here, we conducted a genome-wide CRISPR/Cas9 knockout screen in acute myeloid leukemia (AML) cells in the presence of TAK-243 to identify genes essential for TAK-243 action. We identified BEN domain-containing protein 3 (BEND3), a transcriptional repressor and a regulator of chromatin organization, as the top gene whose knockout confers resistance to TAK-243 in vitro and in vivo. Knockout of BEND3 dampened TAK-243 effects on ubiquitylation, proteotoxic stress, and DNA damage response. BEND3 knockout upregulated the ATP-binding cassette efflux transporter breast cancer resistance protein (BCRP; ABCG2) and reduced the intracellular levelsof TAK-243. TAK-243 sensitivity correlated with BCRP expression in cancer cell lines of different origins. Moreover, chemical inhibition and genetic knockdown of BCRP sensitized intrinsically resistant high-BCRP cells to TAK-243. Thus, our data demonstrate that BEND3 regulates the expression of BCRP for which TAK-243 is a substrate. Moreover, BCRP expression could serve as a predictor of TAK-243 sensitivity.

| S-EPMC8021101 | biostudies-literature

TAK-981

Project description:TAK-981

| PRJNA723842 | ENA

Effect of ubiquitin-activating enzyme inhibition on multiple myeloma cell line MM1.S

Project description:Resistance to proteasome inhibitors has prompted interest in blocking upstream components of the ubiquitin-proteasome pathway for the treatment of multiple myeloma (MM). We therefore evaluated the activity of TAK-243, a novel and specific inhibitor of E1 ubiquitin activating enzyme (UAE) activity, in the MM cell line MM1.S. Treatment of MM1.S with 25 nM TAK-243 for 24 hr caused extensive changes in gene expression, highly uniform between triplicates.

2019-05-01 | GSE126254 | GEO

Adult Caenorhabditis elegans: wild-type (N2) and mir-243 mutant worms

Project description:Transcriptional profiling of N2 vs. mir-243 worms, aiming to identify direct and indirect targets of the microRNA. N2 and mir-243 young-adult worms grown at 20C were analyzed. Three biological replicates with dye-swaps were performed.

2011-09-15 | E-GEOD-20558 | biostudies-arrayexpress

Adult Caenorhabditis elegans: wild-type (N2) and mir-243 mutant worms

Project description:Transcriptional profiling of N2 vs. mir-243 worms, aiming to identify direct and indirect targets of the microRNA.

2011-09-16 | GSE20558 | GEO

Panicum virgatum cultivar:SPR-243

Project description:Panicum virgatum exome capture - SPR-243

| PRJNA446176 | ENA

Homo sapiens strain:ATCC CCL-243

Project description:Human ATCC CCL-243 transcriptome

| PRJNA46859 | ENA

Marchantia polymorpha subsp. ruderalis cultivar:Tak-1 + Tak-2

Project description:Marchantia polymorpha subsp. ruderalis cultivar:Tak-1 + Tak-2 Genome sequencing and assembly