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• W2996975235 abstract "RUVBL1 and RUVBL2 (collectively RUVBL1/2) are essential AAA+ ATPases that function as co-chaperones and have been implicated in cancer. Here we investigated the molecular and phenotypic role of RUVBL1/2 ATPase activity in non-small cell lung cancer (NSCLC). We find that RUVBL1/2 are overexpressed in NSCLC patient tumors, with high expression associated with poor survival. Utilizing a specific inhibitor of RUVBL1/2 ATPase activity, we show that RUVBL1/2 ATPase activity is necessary for the maturation or dissociation of the PAQosome, a large RUVBL1/2-dependent multiprotein complex. We also show that RUVBL1/2 have roles in DNA replication, as inhibition of its ATPase activity can cause S-phase arrest, which culminates in cancer cell death via replication catastrophe. While in vivo pharmacological inhibition of RUVBL1/2 results in modest antitumor activity, it synergizes with radiation in NSCLC, but not normal cells, an attractive property for future preclinical development." @default.
• W2996975235 created "2020-01-10" @default.
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• W2996975235 date "2020-01-01" @default.
• W2996975235 modified "2023-10-18" @default.
• W2996975235 title "RUVBL1/RUVBL2 ATPase Activity Drives PAQosome Maturation, DNA Replication and Radioresistance in Lung Cancer" @default.
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• W2996975235 doi "https://doi.org/10.1016/j.chembiol.2019.12.005" @default.
• W2996975235 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8048778" @default.
• W2996975235 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31883965" @default.
• W2996975235 hasPublicationYear "2020" @default.
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