Sandbox Reserved 1654: Difference between revisions

{{Sandbox_Reserved_ESBS20_}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE -->

[https://en.wikipedia.org/wiki/CPEB CPEB ](Cytoplasmic polyadenylation element binding protein) is present in most vertebrates and invertebrates and can activate or inhibit translation<ref>DOI 10.1016/j.tibs.2007.04.004</ref>. In human body there are 4 different isoforms of CPEB ([https://en.wikipedia.org/wiki/CPEB1 CPEB1] to CPEB4), distributed throughout body in a tissue-dependent manner and which interact differently with mRNA<ref name="publi">DOI 10.1016/j.arr.2012.03.004</ref>.

CPEB protein regulates the length of the polyA tail which allows to control the translation. It binds to mRNA and in association with some factors, can act as a translational repressor or activator, depending on these factors.

All CPEB proteins have a similar structure :

* A N-terminal region which is a regulatory region with phosphorylation and dephosphorylation sites. This region is variable in length and composition.

The N-terminal region of CPEB includes residues in the fourth β strand of the RRM2 domain. Within the linker region between RRM2 and ZZ domains, Leu510 shows long-range interactions with the aromatic ring of Tyr535 in the β2 strand, suggesting that there may be a close interaction between these two domains of CPEB meaning a close interaction between RRM2 and ZZ domains. Disruption of the CPEB-ZZ domain structure could affect the stability of the RRM2 domain structure through loss of the interdomain interface.

CPEB controls the balance between [https://en.wikipedia.org/wiki/Senescence senescence] and proliferation. Indeed, due to its two structural domains in its C-terminal region, it has the capacity to modify mRNA<ref name="publi" />.

RRMs domains allow binding to the [https://en.wikipedia.org/wiki/Cytoplasmic_polyadenylation_element CPE] sequence of mRNA (pyrimidine rich : UUUUUAU), thus ensuring good RNA positioning and high fidelity.

On the other hand, the CPEB can activate the translation. Indeed, in the cytoplasm, there are some repressed or silenced mRNA with a short polyA tail. They can be activated by cytoplasmic polyadenylation thanks to a hormonal stimulation. This stimulation can lead to the phosphorylation of CPEB which increase its affinity with the [https://en.m.wikipedia.org/wiki/Cleavage_and_polyadenylation_specificity_factor CPSF] (Cleavage and Polyadenylation Specificity Factor) and decrease the binding between CPEB and PARN. CPSF binds to the mRNA at the sequence 3’ of the tail of the mRNA (AAUAAA) and recruits the [https://en.wikipedia.org/wiki/Polynucleotide_adenylyltransferase poly(A) polymerase] which leads to the elongation of the polyA tail and therefore to the activation of the translation<ref name="publi" />.  

CPEB proteins play a key role in some diseases, especially in cancers. Indeed, in some humans tumors the level of CPEB 1 is lower than in healthy cells and this leads to the growth of these tumors. An overexpression of CPEB 4 can lead to tumor growth too. Some researches try to find a cancer treatment thanks to CPEB mutations<ref name="publi" />.

<references/>