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cytoplasmic polyadenylation element-binding protein 1 (CPE-binding protein 1, CPE-BP1, hCPEB-1, h-CEBP, CPEB1, CPEB)

Function: 1) sequence-specific RNA-binding protein 2) regulates mRNA cytoplasmic polyadenylation & translation initiation during oocyte maturation, early development & at postsynaptic sites of neurons 3) binds to cytoplasmic polyadenylation element (CPE) 4) in absence of phosphorylation & in association with MASKIN role as repressor of translation of CPE-containing mRNA - repression relieved by phosphorylation or degradation 5) role in transport of CPE-containing mRNA to dendrites - mRNAs may be transported to dendrites in a translationally dormant form & translationally activated at synapses 6) induce polyadenylation & translation of CPE-containing mRNAs in response to NMDA receptor activation 7) interaction with APLP1 promotes local CPE-containing mRNA polyadenylation & translation activation 8) induces assembly of stress granules in the absence of stress 9) interacts with kinesin, dynein, APLP1, APLP2 & APP 10) both phosphorylated & non phosphorylated forms interact with APLP 11) phosphorylated on Ser/Thr by AURKA/STK6 within positions 166 & 197 12) phosphorylation & dephosphorylation on Thr-172 regulates cytoplasmic polyadenylation & translation of CPE-containing mRNAs 13) phosphorylation on Thr-172 by AURKA/STK6 & CAMK2A - activates CPEB1 - may be promoted by APLP1 - increases binding to RNA 14) 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

General

cytoplasmic polyadenylation element-binding protein (CPEB) phosphoprotein

Properties

SIZE: MW = 63 kD entity length = 566 aa COMPARTMENT: cytoplasm MOTIF: Thr phosphorylation site {T172} serine-rich region {178-217} MOTIF: serine residue (SEVERAL) RNP motif NAME: RNP motif SITE: 311-408 FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif NAME: ribonucleoprotein-1 motif FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif ribonucleoprotein-2 motif ribonucleoprotein-2 motif FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif ribonucleoprotein-2 motif stress granule assembly {330-566} MOTIF: RNP motif NAME: RNP motif SITE: 430-511 FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif NAME: ribonucleoprotein-1 motif FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif ribonucleoprotein-2 motif ribonucleoprotein-2 motif FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif ribonucleoprotein-2 motif

Database Correlations

OMIM 607342 UniProt Q9BZB8

References

  1. UniProt :accession Q9BZB8
  2. 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: 17567800
  3. 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: 15175389
  4. 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: 15169862