Question

The activity of transcription factors is frequently regulated by controlling their localization within eukaryotic cells, such that only in response to a given stimulus is the transcription factor transported into the nucleus, where it can activate its target genes. For a transcription factor that has a nuclear localization signal (NLS), describe two mechanisms by which regulated transport can occur.

Answer 1

Ans:

Presence of signalling domain in transcription factor can help in redistribution of TF between cytosol and nucleus. Nuclear Localization Signal is one of such regulatory signal. However inspite of presence of such NLS, the transport to nucleus is also dependent on affinity or interaction of transcription factor or protein with anchor proteins that resides in cytosol or nucleus.

The transcription factor having NLS will interact or get associated with nuclear import factors. In this case TF will show more association or interaction with nuclear import factor rather than export factor, due to this its entry in to nucleus is smooth. TF can also get associated with molecules such as importin and it is regulated in such a way that its association with exportin is very very less. So it can enter in nucleus. YAP1 and nuclear factor of activated T cells ( NFAT) help in such regulation.

Similarly NLS dependent transport of TF is mediated by Phosphorylation. It is the main event in the regulation of NLS dependent transport of proteins or TF.

The TF having NLS can be transported to the nucleus by its interaction with Nuclear Pore complex such as importin molecules. However, the interaction of NLS containing TF with nuclear pore complex can be altered by phosphorylation events of importin molecules. One of the important constituents of the nuclear pore complex is guanine nucleotide-binding protein such as Ran. Phosphorylation events can increase or decrease the accessibility or affinity of importins.