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what is Nuclear Translocation?
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Answer / neha
A key step in all eukaryotic circadian clock mechanisms is
the translocation of a protein or proteins from the
cytoplasm into the nucleus. These proteins are always
components of the negative arm of the cycle, as the
positive elements are always nuclear proteins . The
regulated entry of the proteins dPER and dTIM play an
important part in the Drosophila biological clock.
Both dPER and dTIM contain certain motifs and sequences. In
addition to a PAS domain, both also possess a nuclear
localisation signal and a cytoplasmic localisation domain
(CLD). These CLDs keep the proteins localised in the
cytoplasm. In dPER, the CLD forms a binding site for dTIM.
This means that when dPER and dTIM heterodimerise, the CLD
region of dTIM and dPER are blocked. This allows the two
proteins to be translocated into the nucleus . It appears
that dTIM is only needed for the translocation of dPER, and
the conversion of the dPER/ dTIM heterodimers to nuclear
dPER is a necessary step required to complete the
repression of dclk and cyc to prevent the transcription of
dper and dtim .
In many cases the mechanism by which negative elements are
localised to the nucleus is nuclear. For example in
mammalian clocks, the co-expression of the mCRY and mPER
proteins leads to efficient nuclear localisation. However
mPER 1 and mPER2 can still enter the nucleus without mCRY .
It is thought that the localisation of mPER1 and mPER2
depends on a number of factors including the mCRY proteins,
other proteins (such as casein kinase I Epsilon (which
phosphorylates mPER, keeping mPER1 in the cytoplasm)), and
the phosphorylation states of both mPER and other proteins.
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