Sulfatase activities towards the regulation of cell metabolism and signaling in mammals

Abstract

In higher vertebrates, sulfatases belong to a conserved family of enzymes that are involved in the regulation of cell metabolism and in developmental cell signaling. They cleave the sulfate from sulfate esters contained in hormones, proteins, and complex macromolecules. A highly conserved cysteine in their active site is post-translationally converted into formylglycine by the formylglycine-generating enzyme encoded by SUMF1 (sulfatase modifying factor 1). This post-translational modification activates all sulfatases. Sulfatases are extensively glycosylated proteins and some of them follow trafficking pathways through cells, being secreted and taken up by distant cells. Many proteoglycans, glycoproteins, and glycolipids contain sulfated carbohydrates, which are sulfatase substrates. Indeed, sulfatases operate as decoding factors for a large amount of biological information contained in the structures of the sulfated sugar chains that are covalently linked to proteins and lipids. Modifications to these sulfate groups have pivotal roles in modulating specific signaling pathways and cell metabolism in mammals.

A heterozygous moth genome provides insights into herbivory and detoxification

“…2). In order to function, all sulfatases require posttranslational modification by sulfatase-modifying factor 1 (encoded by SUMF1) 21 , which regulates the sulfatase whose higher activities depend on greater amounts of sulfatase and SUMF1 transcripts 22 . We found that high expression of P. xylostella SUMF1 in third-instar larvae was coupled with significantly higher expression of the GSS1 and GSS2 genes relative to other members of the P. xylostella sulfatase gene family (Fig.…”

A non-conserved miRNA regulates lysosomal function and impacts on a human lysosomal storage disorder

“…Lysosomal desulfation of proteoglycans and other highly sulfated substrates is a prerequisite for their further degradation in the lysosomes 31 . A block in the lysosomal sulfatase activity, causing lysosomal accumulation of sulfated substrates will ultimately disrupt lysosomal function, which can be reflected by an impact on the enzymatic function of other lysosomal enzymes.…”

“…The importance of lysosomal sulfatases in human metabolism is underlined by the study of inherited diseases resulting from defects in sulfatase function 31 . Since SUMF1 is an essential activator of all cellular sulfatases, mutations in this gene cause the most severe disease variant, MSD, in which all sulfatase activity is severely reduced 12,32 .…”

Sulfatase 1 mediates the inhibitory effect of angiotensin II type 2 receptor inhibitor on angiotensin II-induced hypertensive mediator expression and proliferation in vascular smooth muscle cells from spontaneously hypertensive rats

“…Extracellular sulfatases (Sulfs) are hydrolytic enzymes that regulate cell metabolism and signaling [1]. There are 17 distinct sulfatases in humans and 14 sulfatases in rodents.…”

“…There are 17 distinct sulfatases in humans and 14 sulfatases in rodents. Sulfatases are classified as lysosomal, nonlysosomal, and Sulfs, according to their localization [1,2]. Sulfs are designated as heparin sulfate 6-O-endosulfatases, and to date, human, mouse, and rat orthologs have been cloned [3,4].…”