![]() USP7 binds oncogenic targets and controls gene expression through stabilization of NOTCH1 and JMJD3 and ultimately H3K27me3 changes. In turn, USP7 controls NOTCH1 levels through deubiquitination. USP7 is highly expressed in T-ALL and is transcriptionally regulated by NOTCH1. We demonstrate that ubiquitin-specific protease 7 (USP7) interacts with NOTCH1 and controls leukemia growth by stabilizing the levels of NOTCH1 and JMJD3 histone demethylase. To identify and characterize new NOTCH1 druggable partners in T-ALL, we coupled studies of the NOTCH1 interactome to expression analysis and a series of functional analyses in cell lines, patient samples, and xenograft models. Our goal in this work has been to identify enzymes active in T-ALL whose activity could be targeted for therapeutic purposes. However, direct inhibition of these pathways affects healthy tissues and cancer alike. Previous work implicated NOTCH1 and other oncogenes. Chemotherapy treatments show high response rates but have debilitating effects and carry risk of relapse. acute lymphoblastic leukemia (T-ALL) is an aggressive disease, affecting children and adults. 17 Department of Biochemistry and Molecular Genetics, Northwestern University, Chicago, Illinois.1 Department of Biochemistry and Molecular Genetics, Northwestern University, Chicago, Illinois. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois. ![]() 15 Department of Chemistry, Northwestern University, Chicago, Illinois.14 Oncohematology Laboratory, Department of Woman's and Child's Health, University of Padova, Padova, Italy. ![]()
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