The Yeast Ess1 Prolyl Isomerase Controls Swi6 and Whi5 Nuclear Localization

摘要

The prolyl isomerase from Saccharomyces cerevisiae and its human ortholog, Pin1, play critical roles in transcription by regulating RNA polymerase II. In human cells, Pin1 also regulates a variety of signaling proteins, and Pin1 misexpression is linked to several human diseases. To gain insight into /Pin1 function, we carried out a synthetic genetic array screen to identify novel targets of in yeast. We identified potential targets of in transcription, stress, and cell-cycle pathways. We focused on the cell-cycle regulators and , both of which show highly regulated nucleocytoplasmic shuttling during the cell cycle. Surprisingly, did not control their transcription but instead was necessary for their nuclear localization. associated with and in vivo and bound directly to peptides corresponding to their nuclear localization sequences in vitro. Binding by was significant only if the and peptides were phosphorylated at Ser-Pro motifs, the target sites of cyclin-dependent kinases. On the basis of these results, we propose a model in which induces a conformational switch (cis-trans isomerization) at phospho-Ser-Pro sites within the nuclear targeting sequences of and . This switch would promote nuclear entry and/or retention during late M and G1 phases and might work by stimulating dephosphorylation at these sites by the href="http://www.yeastgenome.org/cgi-bin/locus.fpl?dbid=S000001924" data-ga-action="click_feat_suppl" ref="reftype=extlink&article-id=3962490&issue-id=235407&journal-id=1684&FROM=Article%7CFront%20Matter&TO=External%7CLink%7CURI" target="_blank">Cdc14 phosphatase. This is the first study to identify targets of href="http://www.yeastgenome.org/cgi-bin/locus.fpl?dbid=S000003778" data-ga-action="click_feat_suppl" ref="reftype=extlink&article-id=3962490&issue-id=235407&journal-id=1684&FROM=Article%7CFront%20Matter&TO=External%7CLink%7CURI" target="_blank">Ess1 in yeast other than RNA polymerase II.