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

• Published in: The Journal of biological chemistry Vol. 287; no. 13; pp. 10639 - 10649
• Main Authors: Arumugam, Karthik, MacNicol, Melanie C., Wang, Yiying, Cragle, Chad E., Tackett, Alan J., Hardy, Linda L., MacNicol, Angus M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23-03-2012; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Cell Cycle; Cell Cycle - physiology; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cells, Cultured; Developmental Biology; Evolution, Molecular; Mammals; MAP Kinase Signaling System - physiology; mRNA; Musashi; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Oocyte; Oocytes - cytology; Oocytes - metabolism; Protein Biosynthesis - physiology; Proto-Oncogene Proteins c-mos - biosynthesis; Proto-Oncogene Proteins c-mos - genetics; Ribonucleoproteins; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Translation Control; Xenopus; Xenopus laevis; Xenopus Proteins - biosynthesis; Xenopus Proteins - genetics; Xenopus Proteins - metabolism; Xenopus; mRNA; Cell Cycle; Translation Control; Oocyte; Musashi
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M111.300681

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.
The mechanisms that regulate the activity of the mRNA translational regulator, Musashi, are unknown.
Musashi is activated by Ringo/cyclin-dependent kinase and MAP kinase signaling.
Musashi-directed mRNA translation induces MAP kinase signaling and establishes a positive feedback loop to amplify Musashi activity.
Musashi activation to promote translation of target mRNAs presents a potential target for the control of pathological cell cycle progression.