Oxidative stress and heat shock induce a human gene encoding a protein-tyrosine phosphatase

Abstract

REACTIVE oxygen species have been implicated both in the ageing process and in degenerative diseases, including arthritis and cancer^1,2. Bacteria adapt to the lethal effects of oxidants such as hydrogen peroxide by inducing the expression of protective stress genes^3,4. Analogous responses have been identified in human cells. For example, haem oxygenase is a major stress protein in human cells treated with oxidants⁵, and reactive oxygen intermediates activate NF-κB, a transcriptional regulator of genes involved in inflammatory and acute-phase responses⁶. We report here the isolation and characterization of a novel complementary DNA (CL100) corresponding to a messenger RNA that is highly inducible by oxidative stress and heat shock in human skin cells. The cDNA contains an open reading frame specifying a protein of M_r 39.3K with the structural features of a non-receptor-type proteintyrosine phosphatase⁷ and which has significant amino-acid sequence similarity to a Tyr/Ser-protein phosphatase encoded by the late gene H1 of vaccinia virus⁸. The purified protein encoded by the CL100 open reading frame expressed in bacteria has intrinsic phosphatase activity. Given the relationship between the levels of protein-tyrosine phosphorylation, receptor activity, cellular proliferation and cell-cycle control, the induction of this gene may play an important regulatory role in the human cellular response to environmental stress.