Cytoplasmic Polyadenylation Element Binding Proteins in Development, Health, and Disease

Abstract

The cytoplasmic polyadenylation element binding (CPEB) proteins are sequence-specific mRNA binding proteins that control translation in development, health, and disease. CPEB1, the founding member of this family, has become an important model for illustrating general principles of translational control by cytoplasmic polyadenylation in gametogenesis, cancer etiology, synaptic plasticity, learning, and memory. Although the biological functions of the other members of this protein family in vertebrates are just beginning to emerge, it is already evident that they, too, mediate important processes, such as cancer etiology and higher cognitive function. In Drosophila, the CPEB proteins Orb and Orb2 play key roles in oogenesis and in neuronal function, as do related proteins in Caenorhabditis elegans and Aplysia. We review the biochemical features of the CPEB proteins, discuss their activities in several biological systems, and illustrate how understanding CPEB activity in model organisms has an important impact on neurological disease.

A MAPK cascade couples maternal mRNA translation and degradation to meiotic cell cycle progression in mouse oocytes

“…Cytoplasmic polyadenylation of maternal mRNAs requires a cytoplasmic polyadenylation element (CPE) that binds specific trans-acting proteins (Pique et al, 2008). Studies in Xenopus and mouse oocytes found that the CPE-binding protein 1 (CPEB1) mediates cytoplasmic polyadenylation of many CPEcontaining mRNAs (Ivshina et al, 2014). During Xenopus oocyte maturation, phosphorylation of CPEB on several serine/threonine residues is required for early activation of a class of maternal mRNAs, while a large fraction (70-90%) of CPEB1 proteins undergo a polyubiquitylation-dependent degradation in meiosis I (Mendez et al, 2002;Setoyama et al, 2007).…”

Regulation of the Expression of Cytoplasmic Polyadenylation Element Binding Proteins for the Treatment of Cancer

“…It regulates germ cell development, synaptic plasticity and cellular senescence; CREB1 is important for both meiotic progression and mitotic divisions (5,24). CPEB1 neutralizing antibody or dominant-negative mutant forms of this protein inhibit cell division (2,25).…”

“…Twist, a transcription factor, plays an important role in EMT and metastasis (35). CPEB1 interacts with Twist1 mRNA and down-regulates its expression; in the absence of CPEB1, Twist1 mRNA translation is elevated, which leads to EMT and metastasis (5,36). In addition, upon CPEB1 reduction, matrix metalloproteinase 9 (MMP-9) mRNA, which encodes a metastasis-promoting factor, undergoes poly(A) lengthening and enhanced translation (33).…”

“…CPEB1-depleted mammary cells become metastatic to the lung following injection into mouse fat pads, while ectopically expressed CPEB1 prevents metastasis (33). All these results suggest the reduced CPEB1 levels might be related to the tumor formation and metastasis of the transformed breast cells (5). In addition, the CPEB1 knockout animals have significantly faster papilloma formation in carcinogenesis assay than in wild-type animals (2).…”

“…Among these factors, RNAbinding proteins that recognize specific motifs in the 3' untranslated region (3'UTR) of their targets, are important (1, 2, 4). Of these RNA-binding proteins, cytoplasmic polyadenylation element binding protein (CPEB) family are sequence-specific RNA-binding proteins and the key factors controling the elongation of the poly(A) tail and polyadenylation-induced translation (2,5,6). CPEB binds the cytoplasmic polyadenylation element (CPE) in the 3' untranslated regions of responding mRNAs (2, 7-9).…”