Two nuclear localization signals are required for nuclear translocation of nuclear factor 1-A

Nuclear factor 1 (NF1) proteins are encoded by at least four genes (NF1-A, B, C, X). Although DNA-binding and the transcription regulation domains of these proteins are well characterized, the nuclear localization signals (NLSs) are still unknown in all NF1s. We have identified two NLSs in NF1-A, and both are required for full translocation to the nucleus, although one of them itself has a partial translocation ability. These two NLSs are conserved in all four NF1s. Interestingly, three isoforms of NF1-A (NF1-A1, A2, A4) have two NLSs and translocate completely to the nucleus. In contrast, NF1-A3 lacks the second NLS and partially stays in the cytoplasm. Since NF1s construct homodimer and heterodimer, these findings indicate the differential regulations of the NF1 translocation.