Dear Asma, A newly synthesized protein with an NLS is expected to be transported to the nucleus, but it could be retained in the cytoplasm by post-translational modifications or by association with proteins or RNAs, which may mask the nuclear localization sequence, or by association with stable structure in the cytoplasm like the plasma membrane.

Dear Asma,

If a protein localized in the nucleus and cytoplasm too, its allocation is maintened between the two compartments. That means the protein is equally distributed (i can't think any example) or usually it is partitioned differently (active or inactive form).

When an extracellular stimuli (ex. metformin) induce the phosphorylation (PKC) of the endonucleus LKB1, then it exports to the cytoplasm (STRAD+Crm/exportin). The balance of the activated (cytoplasmic) and inactivated (nuclear) protein may be changed between the compartments. The exportation complex "hides" the NLS (importin biding area), that actually is responsible for the importation of inactivated LKB1 from cytoplasm to nucleus after its synthesis in cytoplasm.

If I am wrong, please correct me.

Kind regards,

Philip

Don't be surprised if your protein shuttles back and forth between the nucleus and the cytoplasm, even if it is more concentrated in one compartment than the other. A change in either the import or export rate would then lead to a rapid accumulation in one of the compartments.

When we were looking for an NLS in galectin-3, we noted cytoplasmic accumulation upon some deletions. We later found that the NLS was still intact, and our deletions had made the NES more accessible.