mTOR signaling pathway does not play a role in cytotoxicity induced by SJ6986. (A) Illustration depicting the CRBN-dependent ubiquitin proteasome pathway and its regulatory factors. Genes identified by the genomic CRSIPR/Cas9 screen in at least 1 cell line are labeled in red. Note that well-characterized genes essential for the CRBN E3 ligase complex activity, adaptors, regulators, and effectors are identified by the CRISPR screen. (B-C) Cytotoxicity of SJ6986 and CC-90009 in REH cells with TSC1 or TSC2 knockdown. (D-E) Cytotoxicity of SJ6986 and CC-90009 in U937 cells with TSC1 or TSC2 knockdown. (F-G) Western blot analysis of TSC1 and TSC2 in REH or U937 cells transduced by lentivirus. Signal was normalized to β-actin.