Nuclear transport of peroxisome-proliferator activated receptor α

Peroxisome-proliferator activated receptor alpha (PPAR alpha) is a ligand-activated transcription factor, playing a key role in several essential pathways including lipid metabolism. Although nuclear localization of PPAR alpha is essential for its transactivation activity, mechanisms underlying intracellular traffics of PPAR alpha remain undefined. We here identify and characterize a nuclear localization signal (NLS) residing in the junction between DNA-binding domain and hinge regions of PPAR alpha. The NLS consists of two basic-amino acid clusters locating in the sequence encompassing amino acid residues at 144-187. We evidently show by mutational analysis that the basic residues in this NLS are essential for the nuclear import. Moreover, the PPAR alpha NLS binds well-known nuclear transporters, importin alpha and importin beta, in a manner independent of DNA-binding activity.