Macrophage migration inhibitory factor (MIF) interacts with Bim and inhibits Bim-mediated apoptosis.
The pro-apoptotic Bcl-2 family member Bim acts as a sensor for apoptotic stimuli and initiates apoptosis through the mitochondrial pathway. To identify novel regulators of Bim, we employed the yeast two-hybrid system and isolated the human gene encoding macrophage migration inhibitory factor (MIF), a ubiquitously expressed proinflammatory mediator that has also been implicated in cell proliferation, the cell cycle and carcinogenesis. The interaction between MIF and Bim was confirmed by both in vitro and in vivo protein interaction assays. Intriguingly, protein complexes between MIF and the three major Bim isoforms (BimEL/BimL/BimS) could be detected in HEK293 and K562 cells, especially in cells undergoing apoptosis. Moreover, exogenous expression of MIF partially inhibited Bim-induced apoptosis in HEK293 cells. SiRNA-mediated knockdown of MIF increased apoptosis in K562 cells exposed to the chemical oxidant diamide. Endogenous MIF may regulate the pro-apoptotic activity of Bim and inhibit the release of cytochrome c from mitochondria.
Liu
Lingfeng
L
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, P.R. China.
Chen
Jinzhong
J
Ji
Chaoneng
C
Zhang
Jiayi
J
Sun
Junlei
J
Li
Yao
Y
Xie
Yi
Y
Gu
Shaohua
S
Mao
Yumin
Y
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D007668:Kidney / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008263:Macrophage Migration-Inhibitory Factors; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D045304:Cytochromes c