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. 2022 Feb 16;13:904. doi: 10.1038/s41467-022-28520-4

Fig. 4. Targeted autophagic delivery and degradation of misfolded protein cargoes using AUTOTACs with aggregate-binding warhead.

Fig. 4

a A model illustrating the mode of action of aggregate-targeting AUTOTAC. b Chemical structures of PBA-1105, PBA-1106, Anle138b-F105 and PBA-1105b. c In vitro p62 oligomerization assay in HEK293T cells incubated with the indicated compounds in (b). d WB in HEK293T cells treated with MG132 (1 μM, 24 h), HCQ (10 μM, 24 h), PBA-1105, YTK-1105, and PBA (1 μM, 24 h). e Identical to (d), but with Anle-F105. f ICC of HeLa cells treated with HCQ (10 μM, 24 h), MG132 (2 μM, 18 h) or both in the presence of PBA-1106, YOK-1106 or PBA (1 μM, 24 h). Scale bar, 10 μm. g Quantification of (f) (n = 3, 50 cells). h ICC of HeLa cells treated with Anle138b-F105 (1 μM, 24 h). Scale bar, 10 μm. i Quantification of (h) (n = 3, 50 cells). When indicated, n = 3 biologically independent experiments each counting 50 cells. Data are presented as mean values ± SD where relevant. P-values (from a two-sided unpaired t test): ***P < 7.66E−05. Source data are provided with this paper.