Project description:Identification of critical survival determinants of PDGF-driven proneural glioma. Results provided information about the genes and pathways that are regulated by PDGF signaling in PDGF-driven proneural glioma and led to the assessment of the importance of the USP1-ID2 axis in proneural glioma. Total RNA obtained from PDGF-driven glioma spheroid cells (PDGF-GSC) and primary tumors arising in the Gfap-tTa/Tre-PDGFB mouse model used in our study was analyzed to determine to which subtype of GBM these specimens belonged.

2016-03-22 | E-GEOD-77423 | biostudies-arrayexpress

PDGF Engages an E2F-USP1 Signaling Pathway to Support ID2-mediated Survival of Proneural Glioma Cells.

Project description:Identification of critical survival determinants of PDGF-driven proneural glioma. Results provided information about the genes and pathways that are regulated by PDGF signaling in PDGF-driven proneural glioma and led to the assessment of the importance of the USP1-ID2 axis in proneural glioma. Total RNA was obtained from untreated and Dox treated PDGF-driven glioma spheroid cells (PDGF-GSC) which had been isolated from the Gfap-tTa/Tre-PDGFB mouse model used in our study. The data were analyzed to determine the genes that are regulated by PDGF signaling in PDGF-driven glioma.

2016-03-22 | E-GEOD-77419 | biostudies-arrayexpress

PDGF Engages an E2F-USP1 Signaling Pathway to Support ID2-mediated Survival of Proneural Glioma Cells.

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

2016-03-22 | GSE77424 | GEO

PDGF Engages an E2F-USP1 Signaling Pathway to Support ID2-mediated Survival of Proneural Glioma Cells.

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-03-22 | E-GEOD-77424 | biostudies-arrayexpress

Mus musculus

Project description:PDGF Engages an E2F-USP1 Signaling Pathway to Support ID2-mediated Survival of Proneural Glioma Cells.

| PRJNA310253 | ENA

Mus musculus

Project description:PDGF Engages an E2F-USP1 Signaling Pathway to Support ID2-mediated Survival of Proneural Glioma Cells.

| PRJNA310247 | ENA

Ubiquitinated PCNA drives USP1 synthetic lethality in cancer

Project description:CRISPR Cas9-based functional genomics screening is a powerful approach for identifying and characterizing novel oncology drug targets. Here, we elucidate the synthetic lethal mechanism of deubiquitinating enzyme USP1 in cancers with underlying DNA damage vulnerabilities, specifically BRCA1/2 mutant tumors and a subset of BRCA1/2 wild-type (WT) tumors. In sensitive cells, pharmacological inhibition of USP1 leads to decreased DNA synthesis concomitant with the induction of S-phase-specific DNA damage. Genome-wide CRISPR-Cas9 screens identified RAD18 and UBE2K, which promote PCNA mono- and polyubiquitination respectively, as downstream mediators of USP1 dependency. The accumulation of mono- and polyubiquitinated PCNA following USP1 inhibition was associated with a reduction in total PCNA protein levels. Ectopic expression of WT and ubiquitin-dead K164R PCNA reversed USP1 inhibitor sensitivity. Our results demonstrate, for the first time, that USP1 dependency hinges on the aberrant processing of mono- and polyubiquitinated PCNA. Moreover, this mechanism of USP1 dependency extends beyond BRCA1/2 mutant tumors to a novel subset of BRCA1/2 WT cancer enriched in ovarian and lung lineages. We further show PARP and USP1 inhibition are strongly synergistic in BRCA1/2 mutant cell lines and xenograft models. We postulate USP1 dependency unveils a previously uncharacterized vulnerability linked to post-translational modifications of PCNA. Taken together, USP1 inhibition may represent a unique therapeutic strategy for BRCA1/2 mutant tumors and a subset of BRCA1/2 WT tumors.

2022-09-27 | GSE214121 | GEO

A recombinant lentiviral PDGF-driven mouse model of proneural GBM

Project description:Informed by the genetic alterations observed in human GBM, we engineered a novel, lentiviral injection mediated, mouse model of proneural GBM.

2017-07-12 | GSE99361 | GEO

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