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. Author manuscript; available in PMC: 2019 Dec 18.
Published in final edited form as: Cell Rep. 2019 Oct 1;29(1):118–134.e8. doi: 10.1016/j.celrep.2019.08.090

Figure 7. Selective Small-Molecule-Mediated SHOC2 Degradation in Combination with Trametinib Potently Suppresses MAPK Signaling and Proliferation in KRAS Mutant Cancer Cells.

Figure 7.

(A) Schematic representation of dTAG13-mediated degradation of FKBP12F36V-SHOC2 via CRBN E3 ligase complex ubiquitination and proteasomal degradation.

(B) Representative immunoblot of SHOC2 single-cell KO clones of PA-TU-8902 and MIA PaCa-2 expressing FKBP12F36V-SHOC2 treated with trametinib (10 nM) for 24 h and subsequently treated with dTAG13 compound or DMSO in a time course experiment.

(C) Proliferation assay (CTG) of SHOC2 KO clone, SHOC2 KO clone overexpressing SHOC2-V5, or FKBP12F36V-SHOC2 (PA-TU-8902 and MIA PaCa-2) cells after 6 days of treatment of trametinib (10 nM), dTAG13 (50 nM), or in combination. Bars represent mean of six experimental replicates ± SD.