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Elife. 2016 Nov 1;5. pii: e19298. doi: 10.7554/eLife.19298.

CPEB4 is regulated during cell cycle by ERK2/Cdk1-mediated phosphorylation and its assembly into liquid-like droplets.

Author information

1
Institute for Research in Biomedicine, Barcelona, Spain.
2
The Barcelona Institute of Science and Technology, Barcelona, Spain.
3
Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.

Abstract

The four members of the vertebrate CPEB family of RNA-binding proteins share similar RNA-binding domains by which they regulate the translation of CPE-containing mRNAs, thereby controlling cell cycle and differentiation or synaptic plasticity. However, the N-terminal domains of CPEBs are distinct and contain specific regulatory post-translational modifications that presumably differentially integrate extracellular signals. Here we show that CPEB4 activity is regulated by ERK2- and Cdk1-mediated hyperphosphorylation. These phosphorylation events additively activate CPEB4 in M-phase by maintaining it in its monomeric state. In contrast, unphosphorylated CPEB4 phase separates into inactive, liquid-like droplets through its intrinsically disordered regions in the N-terminal domain. This dynamic and reversible regulation of CPEB4 is coordinated with that of CPEB1 through Cdk1, which inactivates CPEB1 while activating CPEB4, thereby integrating phase-specific signal transduction pathways to regulate cell cycle progression.

KEYWORDS:

CPEB; RNA-binding protein; cell biology; cell cycle; instrinsically disordered region; liquid-like droplets; mRNA translation; xenopus

PMID:
27802129
PMCID:
PMC5089860
DOI:
10.7554/eLife.19298
[Indexed for MEDLINE]
Free PMC Article

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