A novel nuclear import pathway for the transcription factor TFIIS

We have identified a novel pathway for protein import into the nucleus. We have shown that the previously identified but uncharacterized yeast protein Nmd5p functions as a karyopherin, It was therefore designated Kap119p (kar yopherin with M-r of 119 kD). We localized Kap119p to both the nucleus and the cytoplasm, We identified the transcription elongation factor TFIIS as i ts major cognate import substrate. The cytoplasmic Kap119p exists as an app roximately stoichiometric complex with TFIIS. RanGTP, not RanGDP, dissociat ed the isolated Kap119p/TFIIS complex and bound to Kap119p. Kap119p also bo und directly to a number of peptide repeat containing nucleoporins in overl ay assays. In wild-type cells, TFIIS was primarily localized to the nucleus . In a strain where KAP119 has been deleted, TFIIS was mislocalized to the cytoplasm indicating that TFIIS is imported into the nucleus by Kap119p, Th e transport of various substrates that use other karyopherin-mediated impor t or export pathways was not affected in a kap119 Delta strain. Hence Kap11 9p is a novel karyopherin that is responsible for the import of the transcr iption elongation factor TFIIS.