Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ubiquitin-activating enzyme mediates immune escape via suppressing interferon signaling

ABSTRACT: Ubiquitin-activating enzyme mediates immune escape via suppressing interferon signaling

PROVIDER: PRJNA1067613 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Ubiquitin-activating enzyme mediates immune escape via suppressing interferon signaling [bulk RNA-seq]

Project description:Ubiquitin-activating enzyme mediates immune escape via suppressing interferon signaling [bulk RNA-seq]

| PRJNA1067159 | ENA

Ubiquitin-activating enzyme mediates immune escape via suppressing interferon signaling

Project description:How cancer cells escape immune surveillance and resist immunotherapies remain to be elucidated. By screening candidate genes frequently amplified in cancer, we identified expression of ubiquitin-activating enzyme (UBA1) as being the most negatively correlated with signatures related to effector CD8+T cells. High expression of UBA1was strongly predictive of resistance to immune checkpoint blockade (ICB) and poor survival in ICB cohorts. In immunocompetent syngeneic models, but not in immunodeficient models, we found that overexpression ofUba1in cancer cells promoted tumor growth and reduced functional, intratumoral CD8+T cells. Conversely, depletion ofUba1impaired tumor progression, accompanied with increase of functional, intratumoral CD8+T cells. CD8+T cell depletion rescued tumor growth impairment mediated byUba1depletion. Additionally, a selective, small molecule inhibitor of UBA1, TAK-243, delayed tumor growth and augmented ICB in various syngeneic models, in a manner dependent on CD8+T cells. Intratumoral administration of TAK-243 and tumor rechallenge experiments revealed that TAK-243 treatment exhibited a remarkable abscopal effect and provided prolonged protection against cancer, accompanied with elevation of memory CD8+ T cells. Mechanistically, depletion or inactivation of UBA1 stabilized the short-lived interferon (IFN) pathway component, JAK1, upregulated both type-I and -II IFN signaling pathways, and resulted in elevation of key immune modulators, including CXCL9, CXCL10, and MHC-I. Taken together, our data supports that UBA1 mediates cancer immune escape via suppressing interferon signaling and suggests that targeting UBA1 may activate systemic cancer immunity.

2024-10-06 | GSE253880 | GEO

Ubiquitin-activating enzyme mediates immune escape via suppressing interferon signaling [bulk RNA-seq]

2024-10-06 | GSE253810 | GEO

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

Stress granule dynamics are unaffected by ubiquitin activating enzyme inhibition

Project description:SILAC-based quantification of ubiquitin-modified peptides after sodium arsenite treatment in human tissue culture cells. SILAC-based quantification of ubiquitin-modified peptides after ubiquitin-activating enzyme-inhibitor treatment in human tissue culture cells.

| MSV000082933 | MassIVE

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

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

| PRJNA540712 | ENA

Profound effect of a ubiquitin activating enzyme (UAE1) on genomic expression of Toxoplasma gondii

Project description:Profound effect of a ubiquitin activating enzyme (UAE1) on genomic expression of Toxoplasma gondii

| PRJNA1004565 | ENA

Orthogonal ubiquitin transfer identifies ubiquitination substrates under differential control by the two ubiquitin activating enzymes

Project description:Protein ubiquitination is mediated sequentially by ubiquitin activating enzyme E1, ubiquitin conjugating enzyme E2, and ubiquitin ligase E3. Uba1 was thought to be the only E1 until the recent identification of Uba6 as an alternative. To differentiate the biological functions of Uba1 and Uba6, we applied a novel orthogonal ubiquitin transfer (OUT) technology to profile their ubiquitination targets in mammalian cells. By expressing pairs of an engineered ubiquitin and engineered Uba1 or Uba6 that were generated for exclusive interactions, we identified 697 Uba6 targets and 529 Uba1 targets with 258 overlaps. Bioinformatics revealed substantial differences in pathways involving Uba1- and Uba6-specific targets. We demonstrated that polyubiquitination and proteasomal degradation of ezrin and CUGBP1 require Uba6, but not Uba1, and Uba6 is involved in the control of ezrin localization and epithelial morphogenesis. These data reveal the distinctive substrate pools for Uba1 and Uba6 and manifest non-redundant biological roles for Uba6.

2017-07-31 | PXD005513 | Pride

UBE2J1 is the E2 Ubiquitin Conjugating Enzyme Required for Androgen Receptor Degradation

Project description:UBE2J1 is the E2 Ubiquitin Conjugating Enzyme Required for Androgen Receptor Degradation

| PRJNA1003118 | ENA

Interactome of E1 ubiquitin-activating enzymes and of E2 ubiquitin-conjugating enzymes in human HEK293 cells.

Project description:Investigation of E1 ubiquitin-activating enzymes and E2 ubiquitin-conjugating enzymes interactome in human HEK293 cells.

2023-11-14 | PXD042361 | Pride