THE NUCLEAR-LOCALIZATION SIGNAL OF LYMPHOID ENHANCER FACTOR-I IS RECOGNIZED BY 2 DIFFERENTIALLY EXPRESSED SRP1-NUCLEAR LOCALIZATION SEQUENCE RECEPTOR PROTEINS

Proteins are directed to the nucleus by their nuclear localization seq uences (NLSs) in a multistep process, The first step, which is to dock the NLS-containing protein to the nuclear pore, is carried out in par t by a recently identified NLS receptor named Srp1/importin-alpha. Usi ng the high mobility group (HMG) DNA binding domain of human lymphoid enhancer factor-1 (hLEF-1) as bait in a yeast two-hybrid screen, we ha ve identified two different mouse Srp1 proteins (pendulin/importin-alp ha and mSrp1) that each bind to a 9-amino acid sequence in hLEF-1 call ed the B box, We show that the B box of hLEF-1, a region essential for high affinity DNA binding, is also necessary and sufficient for nucle ar localization, lending support to the model that NLSs can function b oth in nuclear transport and DNA binding, Pendulin and mSrp1 are the m ouse homologues of hRch1/hSrp1 alpha/importin-alpha and hSrp1/karyophe rin alpha/NPI-1, respectively, and show considerable sequence divergen ce from each other. We find a surprising and significant difference in the expression pattern of pendulin and mSrp1 mRNA, suggesting that th ese two Srp1 proteins are distinguishable in function as well as seque nce.