Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia

ABSTRACT: Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia

PROVIDER: PRJNA580492 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia

Project description:Splicing alterations are very common in cancer and might affect disease initiation and progression. In several cancers, mutations in splicing factor genes are responsible for aberrant splicing. We show that certain aggressive cancers, such as pediatric T-cell acute lymphoblastic leukemia (T-ALL), have an alternative mechanism for aberrant splicing that involves post-translational regulation of the splicing machinery via deubiquitination. We initially demonstrated that T-ALL presents with extensive exon skipping events affecting proteasomal transcripts, cell cycle and epigenetic regulators. Performing an unbiased genetic screen study for RNA binding proteins, we showed that the serine/arginine-rich splicing factor (SRSF) proteins, controlling exon skipping are critical for T-ALL survival. In our effort to dissect mechanisms of aberrant regulation of SRSF proteins, we focused on the pro-oncogenic deubiquitinase ubiquitin-specific peptidase 7 (USP7) to show it regulates the levels of the SRSF proteins at the post-translational level via active deubiquitination. We further demonstrated that USP7 inhibitors can change the splicing landscape and block T-ALL growth. Our drug studies show that decrease of the levels of SRSF proteins splicing inhibitors sensitize cells to the clinically used splicing inhibitor H3B-8800. Driven by our molecular findings on aberrant splicing of proteasomal transcripts, we demonstrate that H3B-8800 could act synergistically with proteasome inhibitors, paving the way for new therapeutic schemes in pediatric leukemia. Collectively this study provides the proof-of-principle for regulation of splicing factors independently of mutations and via deubiquitination and suggests new therapeutic modalities and combinations in cancer.

| MSV000084383 | MassIVE

Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia [Jurkat_P5091]

Project description:Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia [Jurkat_P5091]

| PRJNA580501 | ENA

Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia [CUTLL1_P5091]

Project description:Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia [CUTLL1_P5091]

| PRJNA580494 | ENA

Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia [Jurkat_shSRSF6]

Project description:Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia [Jurkat_shSRSF6]

| PRJNA580495 | ENA

Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia [Patients I]

Project description:Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia [Patients I]

| PRJNA580496 | ENA

Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia [Patients II]

Project description:Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia [Patients II]

| PRJNA580497 | ENA

Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia [CUTLL1_H3B-8800]

Project description:Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia [CUTLL1_H3B-8800]

| PRJNA580498 | ENA

Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia [Jurkat_H3B-8800 6hr]

Project description:Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia [Jurkat_H3B-8800 6hr]

| PRJNA580499 | ENA

Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia [Jurkat_H3B-8800 24h]

Project description:Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia [Jurkat_H3B-8800 24h]

| PRJNA580500 | ENA

Post-translational regulation of the exon skipping machinery controls aberrant splicing in T cell leukemia [Jurkat_shSRSF6]

Project description:In this study, we show that pediatric T-cell acute lymphoblastic leukemia (T-ALL) has an alternative mechanism for aberrant splicing that involves post-translational regulation of the splicing machinery via deubiquitination.

2020-06-01 | GSE139621 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data