E. Paraskeva et Mw. Hentze, IRON-SULFUR CLUSTERS AS GENETIC REGULATORY SWITCHES - THE BIFUNCTIONAL IRON REGULATORY PROTEIN-1, FEBS letters, 389(1), 1996, pp. 40-43
In the eighties, iron regulatory protein-1 (IRP-1) was identified as a
cytoplasmic mRNA-binding protein that regulates vertebrate cell iron
metabolism. More recently, IRP-1 was found to represent the functional
cytoplasmic homologue of mitochondrial aconitase, a citric acid cycle
enzyme. Its two functions are mutually exclusive and depend on the st
atus of an Fe-S cluster: the (cluster-less) apoIRP-1 binds to RNA, whi
le the incorporation of a cubane 4Fe-4S cluster is required for enzyma
tic activity. Cellular signals including iron levels, nitric oxide and
oxidative stress can regulate between the two activities posttranslat
ionally and reversibly via the EPS cluster, Recent reports suggest tha
t other regulatory proteins may be controlled by similar mechanisms.