Ringo/cyclin-dependent kinase and mitogen-activated protein kinase signaling pathways regulate the activity of the cell fate determinant Musashi to promote cell cycle re-entry in Xenopus oocytes.
Cell cycle re-entry during vertebrate oocyte maturation is mediated through translational activation of select target mRNAs, culminating in the activation of mitogen-activated protein kinase and cyclin B/cyclin-dependent kinase (CDK) signaling. The temporal order of targeted mRNA translation is crucial for cell cycle progression and is determined by the timing of activation of distinct mRNA-binding proteins. We have previously shown in oocytes from Xenopus laevis that the mRNA-binding protein Musashi targets translational activation of early class mRNAs including the mRNA encoding the Mos proto-oncogene. However, the molecular mechanism by which Musashi function is activated is unknown. We report here that activation of Musashi1 is mediated by Ringo/CDK signaling, revealing a novel role for early Ringo/CDK function. Interestingly, Musashi1 activation is subsequently sustained through mitogen-activated protein kinase signaling, the downstream effector of Mos mRNA translation, thus establishing a positive feedback loop to amplify Musashi function. The identified regulatory sites are present in mammalian Musashi proteins, and our data suggest that phosphorylation may represent an evolutionarily conserved mechanism to control Musashi-dependent target mRNA translation.
PubMed ID: 22215682
PMC ID: PMC3323046
Article link: J Biol Chem.
Grant support: P20RR015569 NCRR NIH HHS , P20RR16460 NCRR NIH HHS , R01 HD35688 NICHD NIH HHS , RR020146 NCRR NIH HHS , UL1 RR029884 NCRR NIH HHS , P20 RR015569 NCRR NIH HHS , P30 GM103450 NIGMS NIH HHS , P20 RR015569-10 NCRR NIH HHS , P20 RR016460-10 NCRR NIH HHS
Genes referenced: ccnb1.2 mos msi1 spdya