Jr. Petrulis et al., Subcellular localization of the aryl hydrocarbon receptor is modulated by the immunophilin homolog hepatitis B virus X-associated protein 2, J BIOL CHEM, 275(48), 2000, pp. 37448-37453
The hepatitis B virus X-associated protein 2 (XAP2) is an immunophilin homo
log and core component of the aryl hydrocarbon receptor (AhR). Immunophilin
s are components of many steroid receptor complexes, serving a largely unkn
own function, Transiently expressed AhR.YFP (yellow fluorescent protein) lo
calized to the nuclei of COS-l and NIH-3T3 cells. Go-expression of AhR YFP
with XAP2 restored cytoplasmic localization, which was reversed by 2,3,7,8-
tetrachlorodibenzo-p-dioxin treatment (TCDD), The effect of XAP2 on AhR loc
alization was specific involving a nuclear localization signal-mediated pat
hway. Examination of the ratio of AhR to XAP2 in the AhR complex revealed t
hat similar to 25% of transiently expressed AhR was associated with XAP2, i
n contrast with similar to 100% when the AhR and XAP2 were coexpressed. Str
ikingly, TCDD did not influence these ratios, suggesting that ligand bindin
g initiates nuclear translocation prior to complex dissociation. Analysis o
f endogenous AhR in Hepa-l cells revealed that similar to 40% of the AhR co
mplex was associated with XAP2, predicting observed AhR localization to cyt
oplasm and nuclei. This study reveals a novel functional role for the immun
ophilin-like component of a soluble receptor complex and provides new insig
ht into the mechanism of AhR-mediated signal transduction, demonstrating th
e existence of two structurally distinct and possibly functionally unique f
orms of the AhR.