INOSITOL POLYPHOSPHATE 1-PHOSPHATASE IS PRESENT IN THE NUCLEUS AND INHIBITS DNA-SYNTHESIS

Inositol polyphosphate 1-phosphatase, an enzyme of the phosphatidylino sitol signaling pathway, hydrolyzes the 1-phosphate from inositol 1,4- bisphosphate and inositol 1,3,4-trisphosphate. We have used indirect i mmunofluorescence microscopy, Western blot analysis, and enzyme assays to determine the cellular localization of the enzyme. We find that th e enzyme is present, but not exclusively, in the nucleus of Madin-Darb y bovine kidney cells, and also in COS-7 and HeLa cells that were tran siently transfected with a cDNA encoding bovine inositol polyphosphate 1-phosphatase. DNA synthesis, as measured in COS-7 and HeLa cells tra nsiently overexpressing enzyme, was reduced 59% in cells transfected w ith wild-type enzyme compared with nontransfected cells or cells trans fected with an inactive mutant form of the enzyme. These data demonstr ate that this response is mediated by one of the substrates or product s of inositol polyphosphate 1-phosphatase. We propose that overexpress ed inositol polyphosphate 1-phosphatase degrades a stimulatory inosito l phosphate(s) and thereby inhibits DNA synthesis.