Abstract: Objective Explore the mechanism of TRIM69 inhibits AP1 pathway and down regulates the expression of c-Jun. Methods Co-transfect luciferase reporter plasmids and empty vector or TRIM69 plasmid in HeLa cells or HEK293T cells and make the empty vector group as control, dual-luciferase reporter assay system was used to check the effect of TRIM69 on eight important pathways; over express all length or the deletion mutants of TRIM69 in HEK293T cells and western blot was used to examine the key domain which inhibits the expression of c-Jun; over express TRIM69 in HEK293T cells and then cells were treated with cycloheximide (CHX), MG132 or chloroquine, CHX-chase assay was used to investigate the mechanism of TRIM69 down regulates the expression of c-Jun. Results TRIM69 could inhibit AP1 pathway and down regulate the expression of c-Jun which depends on its RBCC domain (P<0.05). TRIM69 negatively regulates the expression of c-Jun through proteasome degradation (P<0.05). Conclusions TRIM69 could down regulate AP1 pathway and inhibit the expression of c-Jun which depends on proteasome pathway.

Key words: TRIM69, AP1 pathway, c-Jun