POSTER NO: 482

Retinoic acid-induced gene G (RIG-G) executes its function by interacting with Jun activating domain binding protein (JAB1)

Hai-Qing Zhu
Shanghai Institute of Hematology, 197, Rui-Jin Road II

The treatment of acute promyelocytic leukemia (APL) with all trans retinoic acid (ATRA) has set a model for new strategies for cancer therapy. However, the molecular mechanisms of retinoids induced differentiation of APL cells are not yet clarified and warrant further investigation. In the previous work, by using differential display-PCR (DD-PCR) technique, we isolated the RIG-G gene, whose transcriptional expression is undetectable in NB4, an APL cell line, but can be induced by ATRA treatment. RIG-G gene locates at 10q24, codes for a 58-kDa protein containing 490 amino acids with several potential sites for post-translational modification, and presenting a diffuse distribution pattern in the cytoplasm. Database search has revealed a high-level homology between RIG-G and several IFN- stimulated genes. In order to explore the function of RIG-G in retinoid signaling pathways, we focused our efforts on the proteins, which could interact with RIG-G. Recently by means of yeast two- hybrid system, we used RIG-G as bait to screen a cDNA library of human bone marrow, and obtained some candidate clones, one of which is JAB1, a protein initially identified as a co-activator of c-Jun. According to the literature, JAB1 protein could be located in both cytoplasm and nucleus, and could shuttle between both of them. It can facilitate AP1 activation, which plays an important role in cell proliferation and/or apoptosis. And it can also decrease the level of p27Kip1, a protein that can inhibit cell from entering into cell cycle. Our results showed that RIG-G could interfere with the normal function of JAB1. Co-localization of RIG-G and JAB1 suggested that JAB1 could be retained in cytoplasm when co-transfected with RIG-G. We demonstrated that RIG-G could decrease the AP1 activity stimulated by JAB1 in luciferase assay by using an AP1 luciferase reporter vector. We also showed the degradation of p27kip1 caused by JAB1 could be prevented by RIG-G protein expression. Taken together, it is suggested that RIG-G could enhance cell apoptosis by inhibiting AP1 activity and could keep cells from coming into cell cycle by increasing the level of p27kip1. Further research will help us to reveal the biological function of RIG-G more in detail.