NUCLEAR-LOCALIZATION SIGNALS, DNA-BINDING, AND TRANSACTIVATION PROPERTIES OF QUAIL PAX-6 (PAX-QNR) ISOFORMS

We reported previously the characterization of Pax-QNR/Pax-6 products expressed in the avian neuroretina. Five proteins (48, 46, 43, 33, and 32 kDa) were characterized, among which the 33 and 32 kDa proteins ar e devoid of the paired domain. In contrast to the 48-kDa (containing a n alternative paired exon 4a) and 46-kDa proteins exclusively located in the nucleus, the 43- (in which the paired exon 5 is spliced out), 3 3-, and 32-kDa proteins were also found in the cytoplasmic compartment . We report the identification of two nuclear targeting sequences: the basic LKRKLQR region (amino acids 206-212) located in the NH2 terminu s of the homeodomain used by the p43 and 33/32 kDa proteins; and the p aired exon 5 sequence. A case of human aniridia, where arginine 208 of LKRKLQR is mutated into a tryptophan, has been reported recently. We introduced this mutation into the Pax-QNR p46, p43, and p33/32 protein s. No effect on the nuclear localization or in transactivation potenti al of the proteins could be observed. Among the several Pax-QNR isofor ms characterized, only p46 exhibited DNA-binding and transactivating p roperties on the Pax-QNR promoter. Deletions of parts of the protein s howed that the Pax-6 transactivation domain is located in the carboxyl terminus of the protein.