Cyclophilin-40 has a cellular role in the aryl hydrocarbon receptor signaling

Abstract 

Cyclophilin-40 (CyP40) promotes the formation of the gel shift complex that contains the aryl hydrocarbon receptor (AhR), AhR nuclear translocator (Arnt) and dioxin response element (DRE) using baculovirus expressed proteins. Here we reported that CyP40 plays a role in the AhR signaling. When the CyP40 content in MCF-7 cells is reduced, up-regulation of cyp1a1 and cyp1b1 by 3-methylchloranthrene (3MC) is also reduced, suggesting that CyP40 is essential for maximal AhR function. The CyP40 region containing amino acids 186–215, but not the peptidyl-prolyl cis–trans isomerase and tetratricopeptide repeat domains, is essential for forming the AhR/Arnt/DRE complex. CyP40 is found in the cell nucleus after 3MC treatment and appears to promote the DRE binding form of the AhR/Arnt heterodimer.

Abbreviations: AhR, aryl hydrocarbon receptor, Arnt, AhR nuclear translocator, CΔ553, AhR deletion construct with C-terminal 553 amino acids deleted, TH-CΔ553, thioredoxin fusion of CΔ553, DRE, dioxin response element, 3MC, 3-methylchloranthrene, PPIase, peptidyl-prolyl cis–trans isomerase, TPR, tetratricopeptide repeat, βNF, β-napthoflavone, CsA, cyclosporin A, BaP, benzo[a]pyrene, CyP40, cyclophilin-40, ERα, estrogen receptor α, Hsp90, heat shock protein 90

Keywords: Cyclophilin-40, Aryl hydrocarbon receptor, AhR nuclear translocator