CPEB

For the 18th century German composer, see Carl Philipp Emanuel Bach.
Cytoplasmic polyadenylation element binding protein
Properties of CPEBs and their interactions with other proteins in RNP complexes
Identifiers
SymbolCPEB
PfamPF16366
InterProIPR034819
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

CPEB, or cytoplasmic polyadenylation element binding protein, is a highly conserved RNA-binding protein that promotes the elongation of the polyadenine tail of messenger RNA.[1] CPEB is present at postsynaptic sites and dendrites where it stimulates polyadenylation and translation in response to synaptic activity.[2] CPEB most commonly activates the target RNA for translation, but can also act as a repressor,[3] dependent on its phosphorylation state.[4] As a repressor, CPEB interacts with the deadenylation complex and shortens the polyadenine tail of mRNAs.[5] In animals, CPEB is expressed in several alternative splicing isoforms that are specific to particular tissues and functions, including the self-cleaving Mammalian CPEB3 ribozyme. CPEB was first identified in Xenopus oocytes and associated with meiosis;[2] a role has also been identified in the spermatogenesis of Caenorhabditis elegans.[6]

CPEB is involved in closed-loop regulation of mRNAs that keeps them inactive. The closed-loop structure between the 3'UTR and 5'UTR inhibits translation.[7] This has been observed in Xenopus laevis in which eIF4E bound to the 5' cap interacts with Maskin bound to CPEB on the 3' UTR creating translationally inactive transcripts. This translational inhibition is lifted once CPEB is phosphorylated, displacing the Maskin binding site, allowing for the polymerization of the PolyA tail, which can recruit the translational machinery by means of PABP.[8] However, [9] is important to note that this mechanism has been under great scrutiny.[10]

CPEB has been shown to shuttle between the nucleus and cytoplasm.[9] In the nuclei of different organisms, it was found that CPEB helps guide the path of mRNA in the cytoplasm.[2] CPEB was found to be almost exclusively in the c[9] plasm in stage VI Xenopus oocytes.[2] However, a further study on this topic found that there is a substantial amount of CPEB in the nucleus.[9] CPEB can bind with CPE-containing mRNAs in the nucleus, which forces tight translational regulation in the cytoplasm. CPEBs bound to these mRNAs were found to have [11]wer translation efficiency, which is indicative of the translation regulation.

  1. ^ Kim JH, Richter JD (January 2010). "Chapter 278 - Signaling to Cytoplasmic Polyadenylation and Translation". In Bradshaw RA, Dennis EA (eds.). Handbook of Cell Signaling (Second ed.). San Diego: Academic Press. pp. 2317–2321. doi:10.1016/b978-0-12-374145-5.00278-3. ISBN 978-0-12-374145-5.
  2. ^ a b c d Hake LE, Richter JD (November 1994). "CPEB is a specificity factor that mediates cytoplasmic polyadenylation during Xenopus oocyte maturation". Cell. 79 (4): 617–627. doi:10.1016/0092-8674(94)90547-9. PMID 7954828. S2CID 42910508.
  3. ^ de Moor CH, Richter JD (April 1999). "Cytoplasmic polyadenylation elements mediate masking and unmasking of cyclin B1 mRNA". The EMBO Journal. 18 (8): 2294–2303. doi:10.1093/emboj/18.8.2294. PMC 1171312. PMID 10205182.
  4. ^ Mendez R, Barnard D, Richter JD (April 2002). "Differential mRNA translation and meiotic progression require Cdc2-mediated CPEB destruction". The EMBO Journal. 21 (7): 1833–1844. doi:10.1093/emboj/21.7.1833. PMC 125948. PMID 11927567.
  5. ^ Kozlov E, Shidlovskii YV, Gilmutdinov R, Schedl P, Zhukova M (March 2021). "The role of CPEB family proteins in the nervous system function in the norm and pathology". Cell & Bioscience. 11 (1): 64. doi:10.1186/s13578-021-00577-6. PMC 8011179. PMID 33789753.
  6. ^ Luitjens C, Gallegos M, Kraemer B, Kimble J, Wickens M (October 2000). "CPEB proteins control two key steps in spermatogenesis in C. elegans". Genes & Development. 14 (20): 2596–2609. doi:10.1101/gad.831700. PMC 316992. PMID 11040214.
  7. ^ Kang MK, Han SJ (March 2011). "Post-transcriptional and post-translational regulation during mouse oocyte maturation". BMB Reports. 3. 44 (3): 147–157. doi:10.5483/BMBRep.2011.44.3.147. PMID 21429291.
  8. ^ Gilbert S (2010). Developmental Biology. Sunderland, MA: Sinauer Associates, Inc. p. 60. ISBN 978-0-87893-384-6.
  9. ^ a b c d Lin CL, Evans V, Shen S, Xing Y, Richter JD (February 2010). "The nuclear experience of CPEB: implications for RNA processing and translational control". RNA. 16 (2): 338–348. doi:10.1261/rna.1779810. PMC 2811663. PMID 20040591.
  10. ^ Kozak M (November 2008). "Faulty old ideas about translational regulation paved the way for current confusion about how microRNAs function". Gene. 2. 423 (2): 108–115. doi:10.1016/j.gene.2008.07.013. PMID 18692553.
  11. ^ Giangarrà V, Igea A, Castellazzi CL, Bava FA, Mendez R (2015-09-23). Jan E (ed.). "Global Analysis of CPEBs Reveals Sequential and Non-Redundant Functions in Mitotic Cell Cycle". PLOS ONE. 10 (9): e0138794. Bibcode:2015PLoSO..1038794G. doi:10.1371/journal.pone.0138794. PMC 4580432. PMID 26398195.