Nuclear proteins have essential roles in cell proliferation and differ
entiation. We have developed a yeast selection system-the nuclear tran
sportation trap (NTT)-to identify genes encoding nuclear transport sig
nals. Both unknown and previously identified nuclear localization sign
als were identified from a human fetal brain cDNA library. The majorit
y (75%) of the unknown proteins examined were exclusively localized to
the nucleus in COS-7 cells. We propose that NTT is an efficient metho
d for isolating cDNAs that encode nuclear targeted proteins that can b
e applied to the retrieval of novel nuclear proteins and to annotate g
ene function.