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MIF SUMOylation in regulation of its stability and activity during breast cancer progression and metastasis
Author(s) -
Sen Progga,
Zhang XiangDong
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.864.23
Subject(s) - sumo protein , ubiquitin ligase , macrophage migration inhibitory factor , ubiquitin , cancer research , metastasis , cancer cell , downregulation and upregulation , biology , cancer , microbiology and biotechnology , chemistry , cytokine , immunology , biochemistry , genetics , gene
SUMOylation is an essential posttranslational modification that regulates many cellular processes ranging from cell cycle control to protein stability. Dysregulation of SUMOylation has been implicated in various diseases including cancers. Our recent studies revealed that SUMO‐2/3 modification of macrophage migration inhibitory factor (MIF) is greatly increased in metastatic breast cancer cells compared to non‐metastatic control cells. As a pro‐inflammatory and carcinogenic cytokine, MIF acts as a direct link between inflammation and cancer. We further showed that SUMO‐2/3 modification of MIF is positively correlated with its increased levels in metastatic cells compared to non‐metastatic cells, whereas inhibition of SUMOylation by overexpression of SUMO‐specific isopeptidase SENP1 or SENP2 greatly decreases levels of MIF. Furthermore, we demonstrated that MIF is SUMOylated at a single lysine residue, K78, using in vitro SUMOylation assays. MIF is known to be degraded through ubiquitin‐dependent proteolysis and is ubiquitinated at K78, suggesting that MIF SUMOylation can inhibit its ubiquitination and degradation. Lastly, our protein interaction assays have revealed that MIF specifically interacts with SUMO E3 ligase PIAS3. As both PIAS3 and MIF are often upregulated in various types of cancers including breast cancer, it would be very interesting to test whether PIAS3 is the E3 ligase for MIF SUMOylation and increases MIF stability. Hence, characterization of MIF SUMOylation is expected to enrich our understanding of the cross‐talk of SUMO and ubiquitin pathways during breast cancer progression and metastasis. Support or Funding Information Wayne State University Startup Grant American Cancer Society Institutional Grant