We show for the first time that the AhR controls HuR localization, an RNA-binding protein critical in stabilizing Cox-2 mRNA expression levels. A DRE-independent AhR pathway has the potential to be exploited as an anti-inflammatory target, a notion made increasingly feasible with the characterization of selective AhR modulators, a class of AhR ligands without dioxin-associated toxicity. Collectively, these results VE-822 establish that the function of AhR extends beyond its ability to respond to man-made toxicants and solidifies the AhR as part of a regulatory pathway that suppresses inflammatory protein expression. Glutaminase C is known as an important protein in cancer related research. Cancer cells have an altered glucose metabolism known as the Warburg effect. A critical feature of the changed metabolism is that pyruvate no longer enters the citric acid cycle, mandating a new source of metabolites to be formed. Glutaminolysis is a key hallmark of cancer cells where mitochondrial glutaminase catalyzes the conversion of glutamine to glutamate. Important materials such as ATP and nucleotides are produced by further catabolism of glutamate in the Krebs cycle. Glutaminase occurs naturally as two isoforms, namely a liver and a kidney form, as well as a shorter splice variant of KGA referred to as glutaminase C. KGA and GAC are over-expressed in many cancer cells but for breast, lung and prostate tumor cell lines only the GAC specie is found within the mitochondria. The two kidney-type GAs are both phosphate activated enzymes but studies have shown that GAC has a much greater affinity than KGA towards glutamine at higher inorganic phosphate concentrations. Because of GAC��s exclusive location and kinetic properties it has been suggested that this isoform is the key enzyme in mitochondrial metabolism in cancer cells, making it particularly interesting. Knowing the protein structure and its structural behavior in solution is an important step in understanding the mechanism of the GAC isoform and hence improve the understanding of cancer metabolism. It has long been thought that GAC forms a tetramer in order to exhibit activity but the activation mechanism in vivo is still not fully determined. Very little is known about the protein oligomerization states and structural changes in solution. However, recently published crystallographic X-ray structures, determined for a large fragment of the two kidney-type GAs, reveal the dimer- and tetramer-interfaces and most of the active site. Furthermore, it has earlier been 
shown that a change in the enzyme conformation occurs in the area of the tetramer-forming interface which keeps a proposed gating loop to the active site in an open conformation and it has also been shown that Pi can bind in the active site. The structure and mechanism of a large part of the Nterminal and the C-terminal remain unsolved. However, it has been suggested by several studies that significant functionalities reside at the termini. Here we elaborate on the understanding of the solution behavior of GAC by examining the oligomerization state of GAC in solution using small angle X-ray scattering, analytical ultracentrifugation and WY 14643 multiangle light scattering techniques to monitor the effect of Pi titration and increasing protein concentration. We show that the oligomeric state changes with concentration revealing equilibrium between a minimum of three species in solution. It was also shown that the formation of higher oligomers is more pronounced with addition of Pi. The study reveals great conformational freedom of the N- and C-termini of GAC and it was demonstrated that the Cterminal plays a role in the regulation and stabilization of the tetrameric state. We show a correlation between in vitro enzymatic activity of GAC and the oligomeric state.