THE PAG GENE-PRODUCT, A PHYSIOLOGICAL INHIBITOR OF C-ABL TYROSINE KINASE, IS OVEREXPRESSED IN CELLS ENTERING S-PHASE AND BY CONTACT WITH AGENTS INDUCING OXIDATIVE STRESS

The human pag gene product is an inhibitor of the c-abl tyrosine kinas e and belongs to a new family of proteins, We show here that higher le vels of pag gene expression are observed following induction of prolif eration and contact with compounds inducing oxidative stress such as d iethyl maleate and sodium arsenate, A weaker overexpression is seen in a macrophage cell line using hydrogen peroxide or menadione as induce rs. Pag gene expression increases in synchronized cells entering the S phase. This raises the possibility that elevated levels of pag counte ract the cytostatic activity of abl, Treatment of growth arrested cell s with diethyl maleate and sodium arsenate induces pag gene overexpres sion, independently of cell proliferation, Thus, enhanced pag gene exp ression occurs in two cellular events: proliferation and response to o xidative stress. (C) 1998 Federation of European Biochemical Societies .