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. Author manuscript; available in PMC: 2026 Sep 13.
Published in final edited form as: Eur J Med Chem. 2025 Oct 4;301:118228. doi: 10.1016/j.ejmech.2025.118228

Figure 3: PROTAC-induced degradation of TG2 is proteasome-dependent and reduces its enzymatic activity.

Figure 3:

(A, B) Western blot analysis of TG2 levels in SKOV3 cells treated with 10 μM of P374 (A), or P404 and P405 (B) for 24 h, with or without the proteasome inhibitor MG132 (20 μM, 26 h). (C) Quantification of TG2 protein levels from (A) and (B). n = 3 replicates. (D, E) Western blot analysis of TG2 in SKOV3 (D) and OVCAR5 (E) cells treated with a negative control analog of P374 (non-VHL-binding) for 6 and 24 h at 0.1, 1, and 10 μM. Quantification of protein levels is shown in lower panels. (F) Enzymatic activity assay in SKOV3 cells treated with 10 μM of compounds P374, P404, and P405. Treatment with MT4 (20 μM), VHL ligand (10 μM), EDTA was used as negative controls. Protein lysates from TG2 knockdown cells (shTG2) was used as positive control. n = 3 replicates. All values represent means ± SD. *p < 0.05; ***p < 0.001; ****p < 0.0001 by 1 way ANOVA with Tukey post-test.