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Homo sapiens

ABSTRACT: Regulation of stem cell maintenance and lymphoid specification by the ubiquitin ligase Huwe1

PROVIDER: PRJNA338631 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR4019570.fastq.gz	Fastqsanger.gz
	SRR4019571.fastq.gz	Fastqsanger.gz
	SRR4019572.fastq.gz	Fastqsanger.gz
	SRR4019565.fastq.gz	Fastqsanger.gz
	SRR4019566.fastq.gz	Fastqsanger.gz

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Regulation of stem cell maintenance and lymphoid specification by the ubiquitin ligase Huwe1

Project description:The ubiquitin ligase Huwe1 regulates stem cell quiescence, maintenance and lymphoid specification by controlling the expression of N-Myc.

2016-08-18 | GSE85488 | GEO

The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment [microarray]

Project description:We identified the ubiquitin ligase Huwe1 as a crucial regulator of hematopoietic stem cell (HSC) functions. We generated Huwe1 conditional knock-out mice and discovered that the loss of this ligase causes an increased proliferation and stem cell exhaustion, together with a decreased lymphoid specification in vivo. We observed that the ubiquitin ligase Huwe1 is controlling the expression of N-myc at the level of the most immature stem and progenitor hematopoietic populations, mediating the described effects. Hematopoietic stem cells (HSC) from the bone marrow of transgenic animals carrying a N-myc/mCherry fusion gene were sorted according to N-myc expression (defined by mCherry) into N-myc high and low subpopulations. Each of these 2 populations was subjected to microarray gene expression profiling.

2016-08-20 | E-GEOD-85832 | biostudies-arrayexpress

The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment [microarray]

2016-08-20 | GSE85832 | GEO

The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment [high-throughput sequencing]

2016-08-17 | GSE85723 | GEO

The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment

Project description:The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment

| PRJNA339518 | ENA

Mus musculus

Project description:The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment [microarray]

| PRJNA339594 | ENA

Mus musculus

Project description:The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment [high-throughput sequencing]

| PRJNA339174 | ENA

Tumor cell-specific inhibition of MYC function using small molecule inhibitors of the HUWE1 ubiquitin ligase

Project description:Deregulated expression of MYC is a driver of colorectal carcinogenesis, necessitating novel strategies to inhibit MYC function. The ubiquitin ligase HUWE1 (HECTH9, ARFBP1, MULE) associates with both MYC and the MYC-associated protein MIZ1. We show here that HUWE1 is required for growth of colorectal cancer cells in culture and in orthotopic xenograft models. Using high throughput screening, we identify small molecule inhibitors of HUWE1, which inhibit MYC-dependent transactivation in colorectal cancer cells, but not in stem and normal colon epithelial cells. Inhibition of HUWE1 stabilizes MIZ1. MIZ1 globally accumulates on MYC target genes and contributes to repression of MYC-activated target genes upon HUWE1 inhibition. Our data show that transcriptional activation by MYC in colon cancer cells requires the continuous degradation of MIZ1 and identify a novel principle that allows for inhibition of MYC function in tumor cells. MIZ1 and MYC ChIPseq experiments in HUWE1 inhibitor-treated Ls174T cells as well as RNAseq experiments in HUWE1- or MIZ1-depleted Ls174T cells after HUWE1 inhibitor treatment. Sequencing was performed on an Illumina Genome Analyzer IIx.

2014-10-21 | E-GEOD-59223 | biostudies-arrayexpress

E-MTAB-5112

Project description:Regulation of the cardiac transcriptome by the E3 ubiquitin ligase Huwe1.

2016-12-15 | E-MTAB-5112 | ExpressionAtlas

Huwe1 supports B-cell development, B-cell-dependent immunity, somatic hypermutation and class switch recombination by regulating proliferation

Project description:The development and differentiation of B cells is intimately linked to cell proliferation and the generation of diverse immunoglobulin gene (Ig) repertoires. The ubiquitin E3 ligase HUWE1 controls proliferation, DNA damage responses, and DNA repair, including the base excision repair (BER) pathway. These processes are of crucial importance for B-cell development in the bone marrow, and the germinal center (GC) response, which results in the clonal expansion and differentiation of B cells expressing high affinity immunoglobulins. Here, we re-examined the role of HUWE1 in B-cell proliferation and Ig gene diversification, focusing on its involvement in somatic hypermutation (SHM) and class switch recombination (CSR). B-cell-specific deletion of Huwe1 resulted in impaired development, differentiation and maturation of B cells in the bone marrow and peripheral lymphoid organs. HUWE1 deficiency diminished SHM and CSR by impairing B-cell proliferation and AID expression upon activation in vitro and in vivo, and was unrelated to the HUWE1-dependent regulation of the BER pathway. Interestingly, we found that HUWE1-deficient B cells showed increased mRNA expression of Myc target genes upon in vitro activation despite diminished proliferation. Our results confirm that the E3 ligase HUWE1 is an important contributor in coordinating the rapid transition of antigen naïve, resting B cells into antigen-activated B cells and regulates mutagenic processes in B cells by controlling AID expression and the post-transcriptional output of Myc target genes.

2022-12-23 | GSE221351 | GEO

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