CHARACTERIZATION OF THE MAMMALIAN SULFATASE MODIFICATION SYSTEM

We recently identified SUMF1 (SUlfatase Modifying Factor 1), which encodes an activator of all of the sulfatase enzymes. Sulfatases enhance the degradation and the clearance of a large group of compounds from cells. The result of mutations within the SUMF1 gene is the inactivition of all of the sulfatases, with the consequent accumulation of compounds within cells that become toxic and cause tissue damage. SUMF1 is mutated in a disease called Multiple Sulfatase Deficiency. We also discovered a gene homologue of SUMF1 that we called SUMF2. SUMF2 is a negative regulator of SUMF1, and thus of the activities of the sulfatases. We have generated mice with a mutated SUMF2 gene, and we aim to study the phenotype and metabolic defects of this mutation so that we can understand the biological function of SUMF2. We have also seen complexes between SUMF1, SUMF2 and the sulfatases, along with other additional interactors in cells. Thus we want to analyse how these complexes regulate the activity of the free forms of SUMF1, which are most likely to be the only active form. In addition, although the SUMF1 and SUMF2 proteins reside within cells, they are also secreted into the blood. We aim to determine the function of secreted SUMF1 and SUMF2, with regard to their use as agents in the therapy of sulfatase deficiency.