The subcellular localization of Mig1, a transcriptional
repressor responsible for glucose repression of many genes, is regulated
by glucose: it is in the nucleus in the presence of glucose, and in the
cytoplasm in the absence of glucose. The Snf1 protein kinase is thought
to phosphorylate Mig1 upon glucose removal, causing it to leave the
nucleus. This indeed seems to be the case: altering four serines
predicted to be Snf1 kinase phosphorylation sites causes Mig1 to be a
constitutive repressor that is always in the nucleus. The glucose-regulated nuclear transport domain of Mig1 comprises an internal region
of the protein distinct from the DNA binding and repression domains. We
identified in this region a stretch of basic amino acids responsible for
nuclear import. The portion of this sequence that directs nuclear export
appears to contain a novel nuclear export signal, because two leucine-rich sequences similar to known nuclear export signals are not required
for export of Mig1 from the nucleus. Msn5, a protein with homology to
known nuclear exportins and importins, is the probable nuclear exportin
for Mig, because it is required for export of Mig1 from the nucleus.
These results suggest that removal of glucose induces nuclear export of
Mig1 by activating Snf1, which phosphorylates Mig1 and promotes an
interaction with its exportin, Msn5, which then carries Mig1 out of the
nucleus.
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