¹Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

²Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

Correspondence to: JS Lazo, Department of Pharmacology, Biomedical Sciences Tower E1340, University of Pittsburgh, 3550 Terrace and DeSoto Streets, Pittsburgh, PA 15261, USA

One hallmark of neoplasia is the deregulation of cell cycle control mechanisms, which is secondary to altered protein phosphorylation. Dual specificity protein phosphatases uniquely dephosphorylate both phosphoserines/threonines and phosphotyrosines on the same protein substrate. As a class they regulate intracellular signaling through the mitogen activated and stress activated kinases and govern cellular movement through G1/S and G2/M cell cycle checkpoints by affecting the activity of cyclin-dependent kinases. In particular, the Cdc25 phosphatases, which dephosphorylate cyclin-dependent kinases, are overexpressed in many human tumors and this increased expression is associated with a poor prognosis. In addition to expression levels, the intracellular activity of Cdc25 phosphatases is determined by their subcellular distribution and physical proximity to substrates. Small molecules that either inhibit the catalytic activity or alter the subcellular distribution of these dual specificity protein phosphatases could provide effective tools to interrogate the role of phosphorylation pathways and may afford new approaches to the management of cancer. Oncogene (2000) 19, 6607-6612.

tyrosine phosphatases; dual specificity phosphatases; cdc25; cancer