Disease relevance of CPEB1

• Finally, several phenotypes, i.e. progressive oocyte loss and infertility, elicited by the knockdown of CPEB in oocytes resemble those of the human premature ovarian failure syndrome [1].

High impact information on CPEB1

• We show that the synthesis of RINGO/Spy, an atypical activator of cyclin-dependent kinases (cdks), is necessary for CPEB-directed polyadenylation [2].
• CPEB activity requires not only the phosphorylation of S174, but also the synthesis of a heretofore-unknown upstream effector molecule [2].
• Exogenous CPEB restores senescence in the KO MEFs and also induces precocious senescence in wild-type MEFs [3].
• These results demonstrate that a reversible Pum2 interaction controls RINGO/Spy mRNA translation and, as a result, CPEB-mediated cytoplasmic polyadenylation [2].
• Control of cellular senescence by CPEB [3].

Biological context of CPEB1

• In this study we report the cloning of a human cytoplasmic polyadenylation element binding (hCPEB) protein with sequence-specific RNA binding activity [4].
• Our data demonstrate that alternative splicing generates hCPEB mRNAs that encode proteins with a conserved C-terminal RNA binding domain but with different N-terminal regulatory domains [4].
• Here, we demonstrate that the CPE and its binding protein CPEB facilitate mRNA transport to dendrites [5].
• One target of CPEB regulation is myc mRNA, whose unregulated translation in the KO MEFs may cause them to bypass senescence [3].
• Regulated Pumilio-2 binding controls RINGO/Spy mRNA translation and CPEB activation [2].

Anatomical context of CPEB1

• We show that all CPEB1 isoforms are found associated with two previously described cytoplasmic structures, stress granules and dcp1 bodies [6].
• The hCPEB mRNA is expressed in the brain and heart as well as in immature oocytes, consistent with the hypothesis that cytoplasmic polyadenylation may regulate the translation of human mRNAs in both oocytes and somatic cells [4].
• In the hippocampus, mouse GLD2 mRNA colocalizes with CPEB1 and Pumilio1 mRNAs, both of which are likely involved in synaptic plasticity [7].
• To assess the function of CPEB after pachytene, we used the zona pellucida 3 (Zp3) promoter to generate transgenic mice expressing siRNA that induce the destruction of Cpeb mRNA [1].
• While a CPEB knockout (KO) mouse is sterile but overtly normal, embryo fibroblasts derived from this mouse (MEFs) do not enter senescence in culture as do wild-type MEFs, but instead are immortal [3].

Associations of CPEB1 with chemical compounds

• To exert this effect, XGef must retain guanine exchange activity and the interaction with CPEB [8].
• XGef, a guanine exchange factor, is a CPEB-interacting protein involved in the early steps of progesterone-stimulated oocyte maturation [8].
• In vertebrates, enhanced translation of mRNAs in oocytes and early embryos entering M-phase is thought to occur through polyadenylation, involving binding, hyperphosphorylation and proteolytic degradation of Aurora-activated CPEB [9].

Regulatory relationships of CPEB1

• Overexpression of CPEB in neurons promotes the transport of CPE-containing endogenous MAP2 mRNA to dendrites, whereas overexpression of a mutant CPEB that is defective for interaction with molecular motors inhibits this transport [5].
• In analogy to Aurora-A's role in oocyte maturation and the early embryonic cell cycle, here we investigated whether ectopically over-expressed Aurora-A can similarly stimulate polyadenylation of mRNA in human somatic cultured cells by interacting with a human ortholog of cytoplasmic polyadenylation element binding protein, h-CPEB [10].
• Together, these results suggest that CPEB controls senescence and bioenergetics in human cells at least in part by modulating p53 mRNA polyadenylation-induced translation [11].

Other interactions of CPEB1

• In Cpeb knockdown oocytes, Gdf9 RNA has a shortened poly(A) tail and reduced expression [1].
• In Cpeb knockout mice, meiotic progression is disrupted at pachytene due to inhibited translation of synaptonemal complex protein mRNAs [1].

Analytical, diagnostic and therapeutic context of CPEB1

• The microinjection of Inh-2 restores Aurora activation, CPEB hyperphosphorylation and cyclin B translation in enucleated oocytes [9].

References