Wip1 phosphatase: between p53 and MAPK kinases pathways

Abstract

Cells undergoing oncogenic transformation frequently inactivate tumor suppressor pathways that could prevent their uncontrolled growth. Among those pathways p53 and p38MAPK pathways play a critical role in regulation of cell cycle, senescence and cell death in response to activation of oncogenes, stress and DNA damage. Consequently, these two pathways are important in determining the sensitivity of tumor cells to anti-cancer treatment. Wild type p53-induced phosphatase, Wip1, is involved in governance of both pathways. Recently, strategies directed to manipulation with Wip1 activity proposed to advance current day anticancer treatment and novel chemical compounds synthesized to improve specificity of manipulation with Wip1 activity. Here we reviewed the history of Wip1 studies in vitro and in vivo, in genetically modified animal models that support Wip1 role in tumorigenesis through regulation of p53 and p38MAPK pathways. Based on our knowledge we propose several recommendations for future more accurate studies of Wip1 interactions with other pathways involved in tumorigenesis using recently developed tools and for adoption of Wip1 manipulation strategies in anti-cancer therapy.