scholarly journals Mutational analysis of the aryl hydrocarbon receptor (Ahr)-regulated transcriptome in 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and benzo[a]pyrene-treated Hepa-1c1c7 hepatoma cells

2015 ◽  
Author(s):  
MA Sartor
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Mutational Analysis ◽  
Hepatoma Cells ◽  
Aryl Hydrocarbon

The interleukin-6-type cytokine oncostatin M induces aryl hydrocarbon receptor expression in a STAT3-dependent manner in human HepG2 hepatoma cells

FEBS Journal ◽  
2013 ◽  
Vol 280 (24) ◽  
pp. 6681-6690 ◽  
Author(s):  
Natalie Stobbe-Maicherski ◽  
Sandra Wolff ◽  
Christian Wolff ◽  
Josef Abel ◽  
Ulrich Sydlik ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Interleukin 6 ◽  
Hepatoma Cells ◽  
Receptor Expression ◽  
Oncostatin M ◽  
Dependent Manner ◽  
Aryl Hydrocarbon

scholarly journals Interaction of Aryl Hydrocarbon Receptor-interacting Protein-like 1 with the Farnesyl Moiety

2013 ◽  
Vol 288 (29) ◽  
pp. 21320-21328 ◽  
Author(s):  
Anurima Majumder ◽  
Kota N. Gopalakrishna ◽  
Pallavi Cheguru ◽  
Lokesh Gakhar ◽  
Nikolai O. Artemyev
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Solution Structure ◽  
Structural Model ◽  
Mutational Analysis ◽  
Normal Function ◽  
Severe Form ◽  
Scattering Data ◽  
Interacting Protein ◽  
Fk506 Binding Protein ◽  
Aryl Hydrocarbon

Aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) is a photoreceptor specific chaperone of the visual effector enzyme phosphodiesterase-6 (PDE6). AIPL1 has been shown to bind the farnesylated PDE6A subunit. Mutations in AIPL1 are thought to destabilize PDE6 and thereby cause Leber congenital amaurosis type 4 (LCA4), a severe form of childhood blindness. Here, we examined the solution structure of AIPL1 by small angle x-ray scattering. A structural model of AIPL1 with the best fit to the scattering data features two independent FK506-binding protein (FKBP)-like and tetratricopeptide repeat domains. Guided by the model, we tested the hypothesis that AIPL1 directly binds the farnesyl moiety. Our studies revealed high affinity binding of the farnesylated-Cys probe to the FKBP-like domain of AIPL1, thus uncovering a novel function of this domain. Mutational analysis of the potential farnesyl-binding sites on AIPL1 identified two critical residues, Cys-89 and Leu-147, located in close proximity in the structure model. The L147A mutation and the LCA-linked C89R mutation prevented the binding of the farnesyl-Cys probe to AIPL1. Furthermore, Cys-89 and Leu-147 flank the unique insert region of AIPL1, deletion of which also abolished the farnesyl interaction. Our results suggest that the binding of PDE6A farnesyl is essential to normal function of AIPL1 and its disruption is one of the mechanisms underlying LCA.

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