The Dual-Specificity MAP Kinase Phosphatases: critical roles in development and cancer.

International audienceIntracellular signaling by MAP Kinases is involved in many cellular responses and in the regulation of various physiological and pathological conditions. Tight control of the localization and duration of ERK, JNK or p38 MAPK activity is thus a fundamental aspect of cell biology. Several members of the Dual-Specificity Phosphatase (DUSPs) family are able to dephosphorylate MAPK isoforms with different specificity, cellular and tissue localization. Understanding how these phosphatases are themselves regulated during development or in physiological and pathological conditions is therefore fundamental. Over the years, gene deletion and knock-down studies have completed initial in vitro studies and shed a new light on the global and specific roles of DUSPs in vivo. While DUSP1, DUSP2 and DUSP10 appear as crucial players in the regulation of immune responses, other members of the family, like the ERK-specific DUSP6, were shown to play a major role in development. Recent findings on the involvement of DUSPs in cancer progression and resistance will also be discussed