Matches in SemOpenAlex for { <https://semopenalex.org/work/W2952187871> ?p ?o ?g. }
- W2952187871 abstract "Abstract T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease, affecting children and adults. Treatments 1-6 show high response rates but have debilitating effects and carry risk of relapse 5,7,8 . Previous work implicated NOTCH1 and other oncogenes 1,2,9-20 . However, direct inhibition of these pathways affects healthy tissues and cancer alike. Here, we demonstrate that ubiquitin-specific protease 7 (USP7) 21-32 controls leukemia growth by stabilizing the levels of the NOTCH1 and JMJD3 demethylase. USP7 is overexpressed T-ALL and is transcriptionally regulated by NOTCH1. In turn, USP7 controls NOTCH1 through deubiquitination. USP7 is bound to oncogenic targets and controls gene expression through H2B ubiquitination and H3K27me3 changes via stabilization of NOTCH1 and JMJD3. We also show that USP7 and NOTCH1 bind T-ALL superenhancers, and USP7 inhibition alters associated gene activity. These results provide a new model for deubiquitinase activity through recruitment to oncogenic chromatin loci and regulation of both oncogenic transcription factors and chromatin marks to promote leukemia. USP7 inhibition 33 significantly blocked T-ALL cell growth in vitro and in vivo. Our studies also show that USP7 is upregulated in the aggressive high-risk cases of T-ALL and suggest that USP7 expression might be a prognostic marker in ALL and its inhibition could be a therapeutic tool against aggressive leukemia." @default.
- W2952187871 created "2019-06-27" @default.
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- W2952187871 date "2018-01-16" @default.
- W2952187871 modified "2023-10-08" @default.
- W2952187871 title "USP7 cooperates with NOTCH1 to drive the oncogenic transcriptional program in T cell leukemia" @default.
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