Nuclear transport of peroxisome-proliferator activated receptor &alpha;.
Peroxisome-proliferator activated receptor α (PPARα) is a ligand-activated transcription factor, playing a key role in several essential pathways including lipid metabolism. Although nuclear localization of PPARα is essential for its transactivation activity, mechanisms underlying intracellular traffics of PPARα remain undefined. We here identify and characterize a nuclear localization signal (NLS) residing in the junction between DNA-binding domain and hinge regions of PPARα. 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 PPARα NLS binds well-known nuclear transporters, importin α and importin β, in a manner independent of DNA-binding activity.
Department of Biology, Faculty of Sciences, Kyushu University Graduate School, Fukuoka, Japan.
Fumiko
F
Iwamoto
Tomoe
T
Umemoto
Kiyoto
K
Motojima
Yukio
Y
Fujiki
D021581:Active Transport, Cell Nucleus / Q000235:genetics / Q000502:physiology*; D024361:Amino Acids, Basic / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D051379:Mice; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D028901:alpha Karyopherins / Q000378:metabolism; D028961:beta Karyopherins / Q000378:metabolism
D024361:Amino Acids, Basic; D047493:PPAR alpha; D028901:alpha Karyopherins; D028961:beta Karyopherins