In embryonic development, expression of maternal mRNAs regulate cell cycle progression and early developmental processes prior to the onset of zygotic gene transcription. The molecular basis of maternal mRNA translational control is poorly understood. The regulation of protein translation through the cytoplasmic polyadenylation of maternal mRNAs occurs in many organisms including Xenopus, C. elegans, D.melanogaster and the mouse. In Xenopus, progesterone-stimulated cytoplasmic polyadenylation of maternal mRNAs control the synthesis of several key regulators of cell cycle progression (such as Mos, cyclin B1, cyclin B2, cyclin A1 and cdk2). The most extensively characterized of these translationally regulated proteins is the Mos proto-oncogene. Cytoplasmic polyadenylation of Mos mRNA has been shown to be essential for Mos protein synthesis, progesterone-stimulated maturation of Xenopus oocytes and Mos-mediated cytostatic factor activity in mouse oocytes. Despite the recent advances in our knowledge concerning the importance of cytoplasmic polyadenylation in regulation mRNA expression, little is known about the molecular mechanism(s) which mediate this process. The mitogen activated protein kinase (MAPK) signaling pathway (Raf/MEK/MAPK) has been shown to be activated during Xenopus oocyte maturation. Our recent studies have implicated Raf-1 and MEK in the control of Mos protein synthesis through stimulation of the cytoplasmic polyadenylation of Mos mRNA. The studies described in this application will characterize the role of the MAPK signaling pathway in the translational control of Mos and other key regulators of cell cycle regulators of cell cycle progression during vertebrate oocyte maturation. These studies will provide insights into an evolutionary conserved process crucial to early development and yield valuable information on the temporal control of cell cycle progression exerted through the translational regulation of maternal mRNAs. In addition to adding to our understanding of the regulatory pathways governing egg development and fertilization, these studies may provide novel information for the design of therapeutic interventions in the treatment of certain human cancers.
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