NOTCH1-driven UBR7 stimulates nucleotide biosynthesis to promote T cell acute lymphoblastic leukemia
Shashank Srivastava, Umakant Sahu, Yalu Zhou, Ann Hogan, Kizhakke Mattada Sathyan, Justin Bodner, Jiehuan Huang, Kelvin Wong, Natalia Khalatyan, Jeffrey N. Savas, Panagiotis Ntziachristos, Issam Ben‐Sahra, Daniel R. Foltz
Abstract
is overexpressed in NOTCH1-driven T cell acute lymphoblastic leukemia (T-ALL). Impaired nucleotide biosynthesis caused by UBR7 depletion was concomitant with the attenuated cell proliferation and oncogenic potential of T-ALL. Collectively, these results establish UBR7 as a critical regulator of nucleotide metabolism through the regulation of the PRPS enzyme complex and uncover a metabolic vulnerability in NOTCH1-driven T-ALL.
Topics & Concepts
Lymphoblastic LeukemiaNucleotideBiosynthesisLeukemiaCancer researchAcute lymphocytic leukemiaBiologyComputational biologyCell biologyChemistryImmunologyBiochemistryGeneRNA modifications and cancerGenetics and Neurodevelopmental DisordersEpigenetics and DNA Methylation