Chaperone-like activity of macrophage migration inhibitory factor.
Macrophage migration inhibitory factor is a ubiquitous multifunctional cytokine having diverse immunological and neuroendocrine properties. Although this protein is known to be released into the circulation from the secretory granules of anterior pituitary or directly from immune cells as a consequence of stress, its participation in heat stress-induced aggregation of proteins has not yet been reported. We provide here the first evidence that the macrophage migration inhibitory factor possesses chaperone-like properties. It was shown to exist in the form of a mixture of low and high molecular weight oligomers. At heat stress temperatures the large oligomers dissociate into monomers that bind and stabilize thermally denatured malate dehydrogenase and glycogen phosphorylase b and thus prevent aggregation of the model proteins. Similar chaperone-like effects were also observed in the presence of partially purified brain extract containing besides the macrophage migration inhibitory factor a number of ubiquitous hydrophobic low molecular weight proteins identified by N-terminal microsequence analysis. Being highly stable and hydrophobic, the macrophage migration inhibitory factor in combination with other proteins of similar properties may comprise a family of constitutively expressed "small chaperones" that counteract the early onset of stress, around physiological conditions, when heat shock proteins are not abundant.
Cherepkova
Oxana A
OA
A.N. Bakh Institute of Biochemistry, Russian Academy of Sciences, Leninsky Prospect 33, 119071 Moscow, Russia.
Lyutova
Elena M
EM
Eronina
Tatyana B
TB
Gurvits
Bella Ya
BY
D000818:Animals; D002417:Cattle; D024981:Glycogen Phosphorylase / Q000737:chemistry* / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology; D008263:Macrophage Migration-Inhibitory Factors / Q000737:chemistry* / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D020673:Protein Renaturation
D008263:Macrophage Migration-Inhibitory Factors; D018832:Molecular Chaperones; D008291:Malate Dehydrogenase; D024981:Glycogen Phosphorylase