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.
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 722205.
Karthik
K
Arumugam
Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 722205; Center for Translational Neuroscience, University of Arkansas for Medical Sciences, Little Rock, Arkansas 722205.
Melanie C
MC
MacNicol
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 722205.
Yiying
Y
Wang
Interdisciplinary BioSciences Graduate Program, University of Arkansas for Medical Sciences, Little Rock, Arkansas 722205.
Chad E
CE
Cragle
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 722205.
Alan J
AJ
Tackett
Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 722205.
Linda L
LL
Hardy
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 722205; Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 722205; Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas 722205. Electronic address: Angus@UAMS.edu.
Angus M
AM
MacNicol
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D019143:Evolution, Molecular; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008322:Mammals; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology*; D017231:Proto-Oncogene Proteins c-mos / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins; D029867:Xenopus Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D029867:Xenopus Proteins; C119055:ls27 protein, Xenopus; C068598:Msi1 protein, Xenopus; C495329:Mos protein, Xenopus; D017231:Proto-Oncogene Proteins c-mos