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• W2599265625 abstract "Summary Enhancing the tumour suppressive activity of protein phosphatase 2A ( PP 2A) has been suggested to be an anti‐leukaemic strategy. KIAA 1524 (also termed CIP 2A), an oncoprotein inhibiting PP 2A, is associated with disease progression in chronic myeloid leukaemia and may be prognostic in cytogenetically normal acute myeloid leukaemia. Here we demonstrated that the selective proteasome inhibitor, carfilzomib, induced apoptosis in sensitive primary leukaemia cells and in sensitive leukaemia cell lines, associated with KIAA 1524 protein downregulation, increased PP 2A activity and decreased p‐Akt, but not with the proteasome inhibition effect of carfilzomib. Ectopic expression of KIAA 1524, or pretreatment with the PP 2A inhibitor, okadaic acid, suppressed carfilzomib‐induced apoptosis and KIAA 1524 downregulation in sensitive cells, whereas co‐treatment with the PP 2A agonist, forskolin, enhanced carfilzomib‐induced apoptosis in resistant cells. Mechanistically, carfilzomib affected KIAA 1524 transcription through disturbing ELK 1 (Elk‐1) binding to the KIAA 1524 promoter. Moreover, the drug sensitivity and mechanism of carfilzomib in xenograft mouse models correlated well with the effects of carfilzomib on KIAA 1524 and p‐Akt expression, as well as PP 2A activity. Our data disclosed a novel drug mechanism of carfilzomib in leukaemia cells and suggests the potential therapeutic implication of KIAA 1524 in leukaemia treatment." @default.
• W2599265625 created "2017-04-07" @default.
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• W2599265625 date "2017-03-24" @default.
• W2599265625 modified "2023-10-18" @default.
• W2599265625 title "Carfilzomib induces leukaemia cell apoptosis via inhibiting ELK1/KIAA1524 (Elk-1/CIP2A) and activating PP2A not related to proteasome inhibition" @default.
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• W2599265625 doi "https://doi.org/10.1111/bjh.14620" @default.
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