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. 2020 Feb 24;27(8):2484–2499. doi: 10.1038/s41418-020-0517-0

Fig. 6. Distinct impacts on MCL1 prosurvival function upon deleting either NOXA, MARCH5, or MTCH2.

Fig. 6

Steady-state MCL1 protein levels were elevated in both RS4;11 (a) and GRANTA-519 (b) cells transduced with lentiviruses to express Cas9 and sgRNA targeting either NOXA, MARCH5, or MTCH2. The proportion of cells in the transduced populations bearing indels at the sgRNA target sites (as measured by DNA sequencing and reported in Supplementary Table S2) is indicated below the gels. Deleting NOXA rendered RS4;11 (c) and GRANTA-519 (d) cells less sensitive to several triggers of apoptosis, but deleting MARCH5 and MTCH2 did not despite MCL1 being stabilized to comparable levels in all cases. Transduced cell populations from a and b were exposed to the indicated concentrations of ABT-199, RG7388, cisplatin or etoposide for 24–48 h. Cell viability was measured by PI exclusion. Data represent mean ± standard deviation of three independent experiments using two independent sgRNA per gene.