Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2022 Feb 23;41:75. doi: 10.1186/s13046-022-02284-7

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

PMC Copyright notice

Fig. 3 — By inhibiting neddylation, MLN4924 induces a robust UPR in mesothelioma cells. Primary MPM cells derived from 3 different histopathological subtypes, epithelioid (EPI BAP1⁺ UPN7 and EPI BAP1^- UPN11), biphasic (BIP BAP1⁺ UPN14 and BIP BAP1^- UPN16) and sarcomatous (SAR BAP1⁺ UPN22 and SAR BAP^- UPN23) were incubated in fresh medium (CTRL), with 50 μM cisplatin (PT), 0.2 μM MLN4924 (MLN) or their combination (PT+MLN) for 24 h. In panel A and D, we showed the results of the MPM cells that resulted the top-responder cells to the cytotoxic effects of the combination of PT and MLN4924 (according to the results reported in Figure 2): epithelioid (EPI BAP1⁺ UPN7), biphasic (BIP BAP1^- UPN16) and sarcomatous (BAP1⁺ UPN22) MPM cells. A. Cullin 1 neddylation (NED, upper band) was measured by immunoblotting in. Tubulin was used as a loading control. The figure is representative of 1 out of 3 experiments with similar results on EPI BAP1⁺ UPN7, BIP BAP1^- UPN16 and SAR BAP1⁺ UPN22. B. UBE2M activity was measured spectrophotometrically in duplicates. Data are presented as means of 2 primary MPM for each histopathological subtype used + SD (n = 3). ***p < 0.001: treated cells vs CTRL cells; °°°p < 0.001: PT+MLN-treated cells vs PT-treated cells. C. Proteasome activity was measured fluorometrically in duplicates. Data are presented as means of 2 primary MPM for each histopathological subtype used + SD (n = 3). *p<0.05, **p<0.01, ***p < 0.001: treated cells vs CTRL cells. D. Heatmap of the Unfolded Protein Response genes relative expression, in SAR BAP1⁺ UPN 22 MPM cells. Results are expressed in a logarithmic scale. The figure is representative of 1 out of 3 experiments with similar results. Cyan circles: EIF2AK3 and HSPA5 genes. E. EIF2AK3 and HSPA5 proteins were measured by immunoblotting in epithelioid (EPI BAP1⁺ UPN7), biphasic (BIP BAP1^- UPN16) and sarcomatous (BAP1⁺ UPN22) MPM cells. Tubulin was used as a loading control. The figure is representative of 1 out of 3 experiments with similar results