title: DIF-1 induces its own breakdown in Dictyostelium.
abstract: DIF-1 is a novel chlorinated alkyl phenone which induces differentiation of prestalk cells in Dictyostelium discoideum. It is broken down and inactivated by a cytoplasmic enzyme, DIF-1 3(5)-dechlorinase (hereafter referred to as DIF-1 dechlorinase), which is found only in prestalk cells. We show that DIF-1 dechlorinase levels are induced at least 50-fold when cells are treated with DIF-1. This response is rapid--enzyme activity doubles within 15 min and is fully induced within an hour--and occurs early in development, before other prestalk markers can be induced by DIF-1. Maximum inducibility is seen towards the end of aggregation, when DIF-1 dechlorinase is barely detectable in uninduced cells. The dose-dependence reveals a threshold concentration of DIF-1 (15 nM) below which almost no response is seen. Cyclic AMP, which is the chemoattractant during aggregation and plays a key role in later development, suppresses the induction of DIF-1 dechlorinase by DIF-1. We conclude that induction of DIF-1 dechlorinase is one of the first steps on the developmental pathway which leads to prestalk cell differentiation, and suggest that the resulting negative feedback on DIF-1 levels is an important part of the mechanism by which cells decide whether to become prestalk or prespore cells.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: R
authors.initials: R
authors.lastname: Insall
authors.forename: O
authors.initials: O
authors.lastname: Nayler
authors.forename: R R
authors.initials: RR
authors.lastname: Kay
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004023:Dictyostelium / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D004790:Enzyme Induction; D006588:Hexanones / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008190:Lyases / Q000096:biosynthesis*; D008954:Models, Biological; D010088:Oxidoreductases
chemical_list: C075859:DIF-1 3(5)-dechlorinase; D006588:Hexanones; C053433:1-((3,5-dichloro)-2,6-dihydroxy-4-methoxyphenyl)-1-hexanone; D003513:Cycloheximide; D000242:Cyclic AMP; D010088:Oxidoreductases; D008190:Lyases