Identification of intracellular localization signals and of mechanisms underlining the nucleocytoplasmic shuttling of human aryl hydrocarbon receptor repressor.
Two members of the 'AhR family' (a family which is part of the bHLH-PAS superfamily), aryl hydrocarbon receptor (AhR) and AhR repressor (AhRR), originated from a common ancestor and form a regulatory circuit in xenobiotic signal transduction. AhRR is a nucleocytoplasmic shuttle protein, harboring both a nuclear localization signal (NLS) and a nuclear export signal (NES). Because NLS is dominant over NES, AhRR resides predominantly in the nuclear compartment. The NES of AhRR resembles that of AhR in sensitivity to leptomycin B, whereas the NLS of AhRR is monopartite and is, therefore, distinguished from the reported bipartite NLS of AhR. The NLS deletion mutant of GFP-AhRR was transported into the nuclear compartment in the presence of AhR nuclear translocator (Arnt), suggesting the assembly of an AhRR/Arnt heterodimer complex in the cytoplasmic compartment and Arnt-dependent nuclear translocation of this complex.
Kanno
Yuichiro
Y
Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 247-8510, Japan. ykanno@phar.toho-u.ac.jp
Miyama
Yasuo
Y
Takane
Yusuke
Y
Nakahama
Takayuki
T
Inouye
Yoshio
Y
D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006801:Humans; D019913:Nuclear Localization Signals / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*
D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D019913:Nuclear Localization Signals; D029543:Nucleocytoplasmic Transport Proteins; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; C492162:AHRR protein, human