CPEB: a life in translation.

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Trends in Biochemical Sciences (Impact Factor: 13.52). 07/2007; 32(6):279-85. DOI: 10.1016/j.tibs.2007.04.004
Source: PubMed

ABSTRACT Nearly two decades ago, Xenopus oocytes were found to contain mRNAs harboring a small sequence in their 3' untranslated regions that control cytoplasmic polyadenylation and translational activation during development. This cytoplasmic polyadenylation element (CPE) is the binding platform for CPE-binding protein (CPEB), which promotes polyadenylation-induced translation. Since then, the biochemistry and biology of CPEB has grown rather substantially: mechanistically, CPEB nucleates a complex of factors that regulates poly(A) elongation through, of all things, a deadenylating enzyme; biologically, CPEB mediates many processes including germ-cell development, cell division and cellular senescence, and synaptic plasticity and learning and memory. These observations underscore the growing complexities of CPEB involvement in cell function.

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    ABSTRACT: CPEB is a sequence-specific RNA binding protein that regulates cytoplasmic polyadenylation-induced translation. In mouse embryo fibroblasts (MEFs) lacking CPEB, many mRNAs encoding proteins involved in inflammation are mis-regulated. Correlated with this aberrant translation in MEFs, a macrophage cell line depleted of CPEB and treated with lipopolysaccharide (LPS) to stimulate the inflammatory immune response expresses high levels of IL-6, which is due to prolonged nuclear retention of NF-κB. Two proteins involved in NF-κB nuclear localization and IL-6 expression, Iκbα and transforming growth factor-β-activated kinase-1 (TAK1), display excessively low and high steady state levels, respectively, in LPS-treated CPEB-depleted macrophages. However, only TAK1 has an altered synthesis rate that is CPEB-dependent and a double CPEB/TAK1 depletion alleviates high IL-6 production. Peritoneal macrophages isolated from CPEB knockout mice (KO) treated with LPS in vitro also have prolonged NF-κB nuclear retention and produce high IL-6. LPS-injected CPEB KO mice secrete prodigious amounts of IL-6 and other proinflammatory cytokines and exhibit hypersensitivity to endotoxic shock, which are mitigated when the animals are also injected with (5Z)-7-oxozeaenol, a potent and specific inhibitor of TAK1. These data show that CPEB control of TAK1 mRNA translation mediates the inflammatory immune response. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
    Molecular and Cellular Biology 12/2014; 35(3). DOI:10.1128/MCB.00800-14 · 5.04 Impact Factor
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    ABSTRACT: It is widely believed that activity-dependent synaptic plasticity is the basis for learning and memory. Both processes are dependent on new protein synthesis at the synapse. Here, we describe a mechanism how dendritic mRNAs are transported and subsequently translated at activated synapses. Furthermore, we present the players involved in the regulation of local dendritic translation upon neuronal stimulation and their molecular interplay that maintain local proteome homeostasis. Any dysregulation causes several types of neurological disorders including muscular atrophies, cancers, neuropathies, neurodegenerative, and cognitive disorders.
    Frontiers in Molecular Neuroscience 11/2014; 7:84. DOI:10.3389/fnmol.2014.00084


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