IRON REGULATORY PROTEIN-1 IS NOT REQUIRED FOR THE MODULATION OF FERRITIN AND TRANSFERRIN RECEPTOR EXPRESSION BY IRON IN A MURINE PRO-B LYMPHOCYTE CELL-LINE

Iron regulatory proteins (IRPs) are cytoplasmic RNA binding proteins t hat are central components of a sensory and regulatory network that mo dulates vertebrate iron homeostasis. IRPs regulate iron metabolism by binding to iron responsive element(s) (IREs) in the 5' or 3' untransla ted region of ferritin or transferrin receptor (TfR) mRNAs, Two IRPs, IRP1 and IRPZ, have been identified previously, IRP1 exhibits two mutu ally exclusive functions as an RNA binding protein or as the cytosolic isoform of aconitase, We demonstrate that the Ba/F3 family of murine pro-B lymphocytes represents the first example of a mammalian cell lin e that fails to express IRP1 protein or mRNA, First, all of the IRE bi nding activity in Ba/F3-gp55 cells is attributable to IRP2. Second, sy nthesis of IRP2, but not of IRP1, is detectable in Ba/F3-gp55 cells, T hird, the Ba/F3 family of cells express IRP2 mRNA at a level similar t o other murine cell lines, but IRP1 mRNA is not detectable, In the Ba/ F3 family of cells, alterations in iron status modulated ferritin bios ynthesis and TfR mRNA level over as much as a 20- and 14-fold range, r espectively, We conclude that IRP1 is not essential for regulation of ferritin or TfR expression by iron and that IRP2 can act as the sole I RE-dependent mediator of cellular iron homeostasis.