PT  - JOURNAL ARTICLE
AU  - Sun, Chung-Nan
AU  - Cheng, Hsiao-Chun
AU  - Chou, Jui-ling
AU  - Lee, Shen-Yang
AU  - Lin, Ya-Wen
AU  - Lai, Hsing-Lin
AU  - Chen, Hui-Mei
AU  - Chern, Yijuang
TI  - Rescue of p53 Blockage by the A<sub>2A</sub> Adenosine Receptor via a Novel Interacting Protein, Translin-Associated Protein X
AID  - 10.1124/mol.105.021261
DP  - 2006 Aug 01
TA  - Molecular Pharmacology
PG  - 454--466
VI  - 70
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/70/2/454.short
4100  - http://molpharm.aspetjournals.org/content/70/2/454.full
SO  - Mol Pharmacol2006 Aug 01; 70
AB  - Blockage of the p53 tumor suppressor has been found to impair nerve growth factor (NGF)-induced neurite outgrowth in PC-12 cells. We report herein that such impairment could be rescued by stimulation of the A2A adenosine receptor (A2A-R), a G protein-coupled receptor implicated in neuronal plasticity. The A2A-R-mediated rescue occurred in the presence of protein kinase C (PKC) inhibitors or protein kinase A (PKA) inhibitors and in a PKA-deficient PC-12 variant. Thus, neither PKA nor PKC was involved. In contrast, expression of a truncated A2A-R mutant harboring the seventh transmembrane domain and its C terminus reduced the rescue effect of A2A-R. Using the cytoplasmic tail of the A2A-R as bait, a novel-A2A-R-interacting protein [translin-associated protein X (TRAX)] was identified in a yeast two-hybrid screen. The authenticity of this interaction was verified by pull-down experiments, coimmunoprecipitation, and colocalization of these two molecules in the brain. It is noteworthy that reduction of TRAX using an antisense construct suppressed the rescue effect of A2A-R, whereas overexpression of TRAX alone caused the same rescue effect as did A2A-R activation. Results of [3H]thymidine and bromodeoxyuridine incorporation suggested that A2A-R stimulation inhibited cell proliferation in a TRAX-dependent manner. Because the antimitotic activity is crucial for NGF function, the A2A-R might exert its rescue effect through a TRAX-mediated antiproliferative signal. This antimitotic activity of the A2A-R also enables a mitogenic factor (epidermal growth factor) to induce neurite outgrowth. We demonstrate that the A2A-R modulates the differentiation ability of trophic factors through a novel interacting protein, TRAX.