cytoplasmic polyadenylation element-binding protein 1 (CPE-binding protein 1, CPE-BP1, hCPEB-1, h-CEBP, CPEB1, CPEB)
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Function
- sequence-specific RNA-binding protein
- regulates mRNA cytoplasmic polyadenylation & translation initiation during oocyte maturation, early development & at postsynaptic sites of neurons
- binds to cytoplasmic polyadenylation element (CPE)
- in absence of phosphorylation & in association with MASKIN role as repressor of translation of CPE-containing mRNA
- repression relieved by phosphorylation or degradation
- role in transport of CPE-containing mRNA to dendrites
- induce polyadenylation & translation of CPE-containing mRNAs in response to NMDA receptor activation
- interaction with APLP1 promotes local CPE-containing mRNA polyadenylation & translation activation
- induces assembly of stress granules in the absence of stress
- interacts with kinesin, dynein, APLP1, APLP2 & APP
- both phosphorylated & non phosphorylated forms interact with APLP
- phosphorylated on Ser/Thr by AURKA/STK6 within positions 166 & 197
- phosphorylation & dephosphorylation on Thr-172 regulates cytoplasmic polyadenylation & translation of CPE-containing mRNAs
- phosphorylation on Thr-172 by AURKA/STK6 & CAMK2A
- role in plasticity of Schaffer collateral-CA1 synapses[4] Structrure:
- belongs to the CPEB family
- contains 2 RRM domains (RNA recognition motif domains) the 2 RRM domains and the C-terminal region mediate interaction with CPE-containing RNA
Compartment
- cytoplasm, P-bodies & stress granules
- recruited to stress granules upon arsenite treatment
- in dendrites
- localizes in synaptosomes at dendritic synapses of neurons
- strongly enriched in postsynaptic density (PSD) fractions
- transported into dendrites (microtubule-dependent)
- colocalizes in mRNA-containing particles with TACC3, dynein & kinesin
- membrane-associated
- colocalizes at excitatory synapses with members of the polyadenylation & translation complex factors (CPSF, APLP1, TACC3, AURKA/STK6, SYP, etc.) including CPE-containing RNAs
Alternative splicing
named isoforms=4
Expression
- isoform 1 is expressed in immature oocytes, ovary, brain & heart
- isoform 2 is expressed in brain & heart
- isoforms 3 & 4 are expressed in brain
Pathology
- expressed in breast tumors & several tumor cell lines
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/Q9BZB8.html
- ↑ McEvoy M, Cao G, Llopis PM, Kundel M, Jones K, Hofler C, Shin C, Wells DG. Cytoplasmic polyadenylation element binding protein 1-mediated mRNA translation in Purkinje neurons is required for cerebellar long-term depression and motor coordination. J Neurosci. 2007 Jun 13;27(24):6400-11. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17567800
- ↑ Atkins CM, Nozaki N, Shigeri Y, Soderling TR. Cytoplasmic polyadenylation element binding protein-dependent protein synthesis is regulated by calcium/calmodulin-dependent protein kinase II. J Neurosci. 2004 Jun 2;24(22):5193-201. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15175389
- ↑ 4.0 4.1 Alarcon JM, Hodgman R, Theis M, Huang YS, Kandel ER, Richter JD. Selective modulation of some forms of schaffer collateral-CA1 synaptic plasticity in mice with a disruption of the CPEB-1 gene. Learn Mem. 2004 May-Jun;11(3):318-27. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15169862