Inhibition of progesterone-induced Xenopus oocyte maturation by Nm23

The Nm23 protein has been implicated in a wide variety of biological processes, including suppression of metastasis, phytochrome responses in plants, and regulation of differentiation. Here we examine whether Nm23 is involved in Xenopus laevis oocyte maturation. We found that Nm23 is present in oocytes, indicating that it has the potential to be a regulator of maturation. Furthermore, modest overexpression of Nm23 inhibited progesterone-induced oocyte maturation. This maturation-inhibitory activity was shared by both the acidic Nm23-H1 isoform and the basic Nm23-H2 isoform and by Nm23 mutants that lack nucleoside diphosphate kinase activity (Nm23-H1 H118F and Nm23-H2 H118F). Expression of Nm23 proteins delayed the accumulation of Mos and the activation of p42 mitogen-activated protein kinase (MAPK) in progesterone-treated oocytes but had no discernible effect on Mos-induced p42 MAPK activation. Therefore, Nm23 appears to act upstream of the Mos/mitogen-activated protein/extracellular signal-regulated kinase kinase/p42 MAPK cascade. These findings suggest a novel biological role for Nm23.