IQGAP1 promotes tumor progression by stabilizing MCM3/Nrf2 in cholangiocarcinoma

Figure 4 IQGAP1 stabilized MCM3 expression by recruiting USP28 for K48 ubiquitination modification. A: Molecular docking patterns of IQGAP1, MCM3, and USP28 (IQGAP1 in pink, MCM3 in green and USP28 in blue); B: ASP-709, LYS-1653, LYS-1571 of IQGAP1 can form 4 hydrogen bonds with ASP-706, LYS-165, GLU-714 respectively on MCM3. It is proved that there is interaction between them; C: LYS-283, GLU-285, ASP-255, GLU-250 of USP28 can form 4 hydrogen bonds with LYS-248, LYS-177, GLN-386, GLU-185 respectively on MCM3. It is proved that there is interaction between them; D: SER-1084, ASP-1081, GLU-1078, ASP-1090 of IQGAP1 can form 4 hydrogen bonds with SER-205, THR-207, ARG-247, LYS-262, LYS-99 respectively on USP28. It is proved that there is interaction between them; E: The altered protein amount of MCM3 regulated by USP28 could be terminated by the addition of the proteasome inhibitor MG132; F: The addition of actinotide inhibited intracellular protein synthesis and faster degradation of MCM3 was observed upon knockdown of USP28 and lower degradation of MCM3 was observed upon overexpression of USP28; G: The expression of USP28 was inversely proportional to the ubiquitination level of MCM3; H: USP28 prevented MCM3 degradation through K48 ubiquitin chain-dependent breakout. NC: Negative control; si: Silence; WT: Wild type; UB: Ubiquitination; IP: Immunoprecipitation.