Fig. 4: Proteasome activity and inhibition in cell lines and TET tissue and the relevance of PSMB8 in carfilzomib treatment.
From: Proteasome inhibition as a potential therapeutic target in thymic cancer
A ABP fluorescent labeled constitutive and immunoproteasome subunit activity in protein lysates of TET showing a strong immunoproteasome activity in TET. B The addition of carfilzomib to lysates of 1889c cells and two TET patient tissues samples (P1 (type B3) and P2 (type B2)) resulted in a strong inhibition of the constitutive and the immunoproteasome. C A single treatment with increasing concentration of immunoproteasome specific inhibitor ONX (50 - 250 nM) or combined with a sublethal concentration of carfilzomib (12.5 nM) of 1889c over 48 hours. D IFN-γ (100 IU/ml, 48 hours) induced immunoproteasome subunits in 1889c, MP57, HCC15, MCF7, and LNCaP and (E) significantly increased the response to carfilzomib. F Knockdown of PSMB8 and PSMB10 with two specific siRNAs (si1, si2) in 1889c (upper and lower panels left) and MP57 (upper and lower panels right) significantly decreased the response to carfilzomib. G Strong correlation between the PSMB5:PSMB8 protein expression ratio and the response to carfilzomib in Raji, 1889c, MP57, PC3, HCC15, LNCaP, and CAKI2 cells (R2 = 0.9555, p < 0.0001). **p < 0.01; ***p < 0.001; ****p < 0.0001.
