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. 2023 May 19;299(6):104838. doi: 10.1016/j.jbc.2023.104838

Figure 9.

Figure 9

Specificity of suppressor mutations for attenuating diverse CADASIL NOTCH3 mutations. Suppressor mutants in EGF1 (C65S), EGF2 (C117S), and EGF3 (C146S) from Figure 8 were assessed for ability to normalize gel mobility shifts of CADASIL NOTCH3 mutations C49Y, R90C, and C155Y (located within EGF repeats 1, 2, and 3; see labels under each panel). We assessed if suppressors preferred to act on mutations within the same EGF repeat or, alternatively, were capable of acting across EGF repeats. A, effects of suppressor mutation C65S from EGF repeat 1. Bottom labels indicate the EGF repeat location of the suppressor and the CADASIL mutation. WT, single, and double mutation gene products underwent gel shift analysis (top panel) and quantification (middle panel). B, the same analysis as in (A), except that suppressor mutation C117S from EGF repeat 2 was tested in combination with three CADASIL mutations. C, the same analysis as in (A) but focusing on suppressor mutation C146S. Results are from at least three independent experiments. Comparisons were made between gel shifting of each single mutant (CADASIL NOTCH3 mutations) and the same mutant combined with a suppressor (three comparisons per panel); pair wise comparisons with ∗p < 0.05.