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- W4306178384 abstract "Previously, we discovered that deletion of c-Rel in the Eµ-Myc mouse model of lymphoma results in earlier onset of disease, a finding that contrasted with the expected function of this NF-κB subunit in B-cell malignancies. Here we report that Eµ-Myc/cRel-/- cells have an unexpected and major defect in the CHK1 pathway. Total and phospho proteomic analysis revealed that Eµ-Myc/cRel-/- lymphomas highly resemble wild-type (WT) Eµ-Myc lymphomas treated with an acute dose of the CHK1 inhibitor (CHK1i) CCT244747. Further analysis demonstrated that this is a consequence of Eµ-Myc/cRel-/- lymphomas having lost expression of CHK1 protein itself, an effect that also results in resistance to CCT244747 treatment in vivo. Similar down-regulation of CHK1 protein levels was also seen in CHK1i resistant U2OS osteosarcoma and Huh7 hepatocellular carcinoma cells. Further investigation revealed that the deubiquitinase USP1 regulates CHK1 proteolytic degradation and that its down-regulation in our model systems is responsible, at least in part, for these effects. We demonstrate that treating WT Eµ-Myc lymphoma cells with the USP1 inhibitor ML323 was highly effective at reducing tumour burden in vivo. Targeting USP1 activity may thus be an alternative therapeutic strategy in MYC-driven tumours." @default.
- W4306178384 created "2022-10-14" @default.
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- W4306178384 date "2022-10-14" @default.
- W4306178384 modified "2023-10-10" @default.
- W4306178384 title "Regulation of CHK1 inhibitor resistance by a c-Rel and USP1 dependent pathway" @default.
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- W4306178384 cites W1980246358 @default.
- W4306178384 cites W1985701259 @default.
- W4306178384 cites W1999982643 @default.
- W4306178384 cites W2008055481 @default.
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- W4306178384 cites W2012626734 @default.
- W4306178384 cites W2014925652 @default.
- W4306178384 cites W2015946135 @default.
- W4306178384 cites W2020045401 @default.
- W4306178384 cites W2033221504 @default.
- W4306178384 cites W2034563330 @default.
- W4306178384 cites W2036826205 @default.
- W4306178384 cites W2042073539 @default.
- W4306178384 cites W2054468210 @default.
- W4306178384 cites W2059427680 @default.
- W4306178384 cites W2059640124 @default.
- W4306178384 cites W2063441831 @default.
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- W4306178384 cites W2110802822 @default.
- W4306178384 cites W2111500154 @default.
- W4306178384 cites W2117280290 @default.
- W4306178384 cites W2125197632 @default.
- W4306178384 cites W2126415922 @default.
- W4306178384 cites W2134071049 @default.
- W4306178384 cites W2134503721 @default.
- W4306178384 cites W2134558237 @default.
- W4306178384 cites W2136426653 @default.
- W4306178384 cites W2137026987 @default.
- W4306178384 cites W2145264022 @default.
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- W4306178384 cites W2157145997 @default.
- W4306178384 cites W2157350623 @default.
- W4306178384 cites W2157918066 @default.
- W4306178384 cites W2157942810 @default.
- W4306178384 cites W2158957674 @default.
- W4306178384 cites W2162923414 @default.
- W4306178384 cites W2164419903 @default.
- W4306178384 cites W2169630006 @default.
- W4306178384 cites W2172258604 @default.
- W4306178384 cites W2179438025 @default.
- W4306178384 cites W2195933887 @default.
- W4306178384 cites W2197124664 @default.
- W4306178384 cites W2235521964 @default.
- W4306178384 cites W2263499430 @default.
- W4306178384 cites W2500053863 @default.
- W4306178384 cites W2583517964 @default.
- W4306178384 cites W2592811885 @default.
- W4306178384 cites W2739354418 @default.
- W4306178384 cites W2768167146 @default.
- W4306178384 cites W2789509086 @default.
- W4306178384 cites W2805182314 @default.
- W4306178384 cites W2809275164 @default.
- W4306178384 cites W2900569176 @default.
- W4306178384 cites W2904294837 @default.
- W4306178384 cites W2906377468 @default.
- W4306178384 cites W2943380091 @default.
- W4306178384 cites W2944784952 @default.
- W4306178384 cites W2953041081 @default.
- W4306178384 cites W2995533802 @default.
- W4306178384 cites W3009974692 @default.
- W4306178384 cites W3026618910 @default.
- W4306178384 cites W3032975128 @default.