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Functional Association of Nm23‐H1 Tumor Suppressor with Macrophage Migration Inhibitory Factor (MIF)
Author(s) -
Ha Hyunjung,
Jung Haiyoung,
Seong HyunA
Publication year - 2007
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.21.5.a382-d
Subject(s) - macrophage migration inhibitory factor , mutant , suppressor , kinase , cell growth , carcinogenesis , microbiology and biotechnology , chemistry , biology , cancer research , biochemistry , cytokine , immunology , gene
Here we report that Nm23‐H1 tumor suppressor is an interacting partner of MIF in cells. The use of Nm23‐H1 mutants (C4S, C109S, and C145S) and MIF mutants (C57S, C60S, and C81S) revealed that this interaction was significantly affected by C145S mutant of Nm23‐H1 and C60S mutant of MIF, but not other Nm23‐H1 and MIF mutants, suggesting that a disulfide linkage involving Cys 145 of Nm23‐H1 and Cys 60 of MIF is responsible for Nm23‐H1‐MIF complex formation. In terms of biological significances, coexpression of MIF significantly inhibited Nm23‐H1 biochemical activities such as autophosphorylation, phosphotransferase activity, and nucleoside‐diphosphate kinase activity, whereas Nm23‐H1‐induced cell growth in HaCaT cells was enhanced by MIF. On the other hand, in addition to the inhibition of MIF‐induced proliferation in NIH/3T3 cells, Nm23‐H1 coexpression stimulated the D‐dopachrome tautomerase activity of MIF. Moreover, Nm23‐H1 rescued MIF‐induced suppression of p53 activity and potentiated p53‐mediated apoptosis though the enhancement of p53 stability and stimulation of p53 nuclear translocation. These results indicate that Nm23‐H1 may be a potential negative modulator of MIF that is implicated in the regulation of inflammation and tumorigenesis.