| First Author | Fingerle-Rowson G | Year | 2009 |
| Journal | Mol Cell Biol | Volume | 29 |
| Issue | 7 | Pages | 1922-32 |
| PubMed ID | 19188446 | Mgi Jnum | J:147772 |
| Mgi Id | MGI:3842070 | Doi | 10.1128/MCB.01907-08 |
| Citation | Fingerle-Rowson G, et al. (2009) A tautomerase-null macrophage migration-inhibitory factor (MIF) gene knock-in mouse model reveals that protein interactions and not enzymatic activity mediate MIF-dependent growth regulation. Mol Cell Biol 29(7):1922-32 |
| abstractText | Macrophage migration-inhibitory factor (MIF) is an upstream regulator of innate immunity and a potential molecular link between inflammation and cancer. The unusual structural homology between MIF and certain tautomerases, which includes both a conserved substrate-binding pocket and a catalytic N-terminal proline (Pro1), has fueled speculation that an enzymatic reaction underlies MIF's biologic function. To address the functional role of the MIF tautomerase activity in vivo, we created a knock-in mouse in which the endogenous mif gene was replaced by one encoding a tautomerase-null, Pro1-->Gly1 MIF protein (P1G-MIF). While P1G-MIF is completely inactive catalytically, it maintains significant, albeit reduced, binding to its cell surface receptor (CD74) and to the intracellular binding protein JAB1/CSN5. P1G-MIF knock-in mice (mif(P1G/P1G)) and cells derived from these mice show a phenotype in assays of growth control and tumor induction that is intermediate between those of the wild type (mif(+/+)) and complete MIF deficiency (mif(-)(/)(-)). These data provide genetic evidence that MIF's intrinsic tautomerase activity is dispensable for this cytokine's growth-regulatory properties and support a role for the N-terminal region in protein-protein interactions. |
