Small ubiquitin-like modifier (SUMO) family proteins regulate target protein functions by post-translational modification. However, a potent and selective inhibitor to target the SUMO pathway has been lacking. Here we describe ML-792, the first mechanism-based SUMO-activating enzyme (SAE) inhibitor with nanomolar potency in cellular assays. ML-792 selectively blocks SAE enzyme activity and total SUMOylation, which leads to reduced cancer cell proliferation. Moreover, induction of the MYC oncogene increased the ML-792 mediated viability effect in cancer cells, indicating potential application of SAE inhibitors in MYC-amplified tumors. Using ML-792, we further explored the critical roles of SUMOylation in mitotic progression and chromosome segregation. Furthermore, expression of an SAE catalytic subunit (UBA2) mutant S95N/M97T rescued SUMOylation loss and the mitotic defect induced by ML-792, confirming the selectivity of ML-792. As a potent and selective SAE inhibitor, ML-792 provides rapid loss of endogenously SUMOylated proteins allowing for novel insights into SUMO biology. Overall design: RNA-SEQ was used to analyze changes in mRNA profiles of human colon and breast cancer cells treated with ML00754792 SAEi
Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor.
Cell line, Treatment, Subject, Time
View SamplesIn the developing embryo, haematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros (AGM) region but the molecular regulation of this process is poorly understood. Recently, the progression from E9.5 to E10.5 and polarity along the dorso-ventral axis have been identified as clear demarcations of the supportive HSC niche. To identify novel secreted regulators of HSC maturation, we performed RNA-sequencing over these spatio-temporal transitions in the AGM region, and supportive OP9 cell line. Overall design: RNA-sequencing profiles of the aorta-gonad-mesonephros region from E9.5 embryos and E10.5 embryos sub-dissected into dorsal (AoD), ventral (AoV) and urogenital ridges (UGR) and pooled from between 15 and 34 embryos in three separate experiments.
A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation.
Specimen part, Subject
View SamplesIn the developing embryo, haematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros (AGM) region but the molecular regulation of this process is poorly understood. Recently, the progression from E9.5 to E10.5 and polarity along the dorso-ventral axis have been identified as clear demarcations of the supportive HSC niche. To identify novel secreted regulators of HSC maturation, we performed RNA-sequencing over these spatio-temporal transitions in the AGM region, and supportive OP9 cell line. Overall design: RNA-sequencing profiles of OP9 cells grown in flat, submersed culture or reaggregate and cultured at the liquid-gas interface were compared.
A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation.
Specimen part, Cell line, Subject
View SamplesWe have characterized gene expression changes in HeLa cells following long term depletion of Cyclin T2 or Cyclin T1 using shRNA
Limited redundancy in genes regulated by Cyclin T2 and Cyclin T1.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors.
No sample metadata fields
View SamplesParental MM6 cells, as an additional control, were treated with LPS and PMA. Genes affected by the treatments were identified.
Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors.
No sample metadata fields
View SamplesCyclin T1-dependent genes in PMA-activated MM6 cells.
Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors.
No sample metadata fields
View SamplesCyclin T1-dependent genes in LPS-activated MM6 cells.
Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors.
No sample metadata fields
View SamplesCyclin T1-dependent genes in activated Jurkat cells.
Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors.
No sample metadata fields
View SamplesCyclin T1-dependent genes in non-activated Jurkat cells.
Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors.
No sample metadata fields
View Samples