Fig. 2
From: The emerging roles of SUMOylation in pulmonary diseases
SUMOylation-mediated regulation in pulmonary diseases
(A) In SARS-CoV-2 infected cells, the coronavirus N protein could be modified by SUMO1, promoting SARS-CoV replication. In addition, ACE2, the cellular receptor protein for the virus, could interact with SUMO3 by PIAS4 to suppress its degradation;
(B) In HPMECs of HPH, SENP1 regulates the abundance and nuclear-cytoplasmic distribution of KLF15 through SUMOylation/deSUMOylation, which is a process sensitive to hypoxia;
(C) In HBE cells of COPD, S-CMC can upregulate HDAC activity by blocking CSE-induced SUMO1 modification of HDAC2, making it a potential therapeutic drug for COPD. In smokers’ alveolar macrophages, SUMO2/3 modified DICER inhibits the maturation of miRNAs;
(D) In HDM-induced allergic asthma airway epithelium, CBX4 boosts the transcription of MEX-3B by increasing the SUMOylation of general transcription factor TFII-I, which in turn enhances the translation of lfTSLP by binding to its mRNA;
(E) In lung MDSCs isolated from mouse models of K. pneumoniae (KP) pneumonia, the CL-mediated K107 SUMOylation of PPARγ inhibits the production of IL-10 through PIAS2 recruitment which requires concurrent activation of PPAR S112 phosphorylation by JNK-MAPK. Additionally, in lung epithelial cells, Klebsiella induces the expression of CSN5 to prevent the NEDDylation of the Cullin-1 subunit of the ubiquitin ligase complex and thus suppresses SENP2 ubiquitylation and subsequent degradation. In macrophages, TLR4-TRAM-TRIF-induced IFN decreases the SUMOylation levels via let-7 miRNAs;
(F) In NSCLCs, Ubc9/PIAS4-mediated Slug SUMOylation and subsequent HDAC1 recruitment lead to the hypoxia-induced lung cancer metastasis;
(G) In BDP, SENP1 controls the expression and distribution of SIRT1 by deSUMOylating it in the hyperoxic alveolar epithelial cell damage model, leading to increased Ac-p53 expression levels and promoting cell apoptosis;
(H) In lung epithelial cells of IPF, FIEL1 targets PIAS4 and causes its degradation, promoting the SUMOylation of SMAD3 and TGF-β signaling;