Study On The Sumoylation And Function Of MGEA6

Meningioma expressed antigen 6（MGEA6）was originally identified as a novel immunoreactive antigen in meningioma patients.Antibodies against MGEA6 were also detected in the sera from cutaneous T cell lymphoma and glioblastoma patients.MGEA6 expression is higher in many tumor tissues than in normal tissues.Although MGEA6 has been implicated as an oncogene,its underlying mechanism in tumorigenesis has not been elucidated.In this research,MGEA6 is apparently overexpressed in several highly malignant cancer cell lines,but its expression is relatively low in benign or normal cell lines.MGEA6 expression is also elevated in hepatocellular carcinoma（HCC）tissues than normal tissues.In addition,most HCC patients develop MGEA6 antibodies.We demonstrate that MGEA6 plays a crucial role in HCC cell proliferation.HEK293 cells and Changliver cells expressing MGEA6 proliferate faster than control cells.Knockdown of MGEA6 significantly suppresses the proliferation of BEL-7402 cells and leads to the formation of much smaller colonies on soft agar.MGEA6 interacts with UBC9,the unique SUMO conjugation enzyme of SUMOylation pathway.The interaction between MGEA6 and UBC9 is originally identified by yeast two-hybrid screening.Immunoprecipitation assay and in vitro binding assay show that MGEA6 interacts with UBC9 both in vivo and in vitro.In this study,we show that MGEA6 is SUMOylated at Lys 153 and Lys494 residues by SUMO1.MGEA6 K153R/K494R mutant loses the capacity to improve cell proliferation.Overexpression of MGEA6 induces NF-κB activation,however,MGEA6 mutant no longer induces the activation of NF-κB signaling pathway.These results indicate that SUMOylation of MGEA6 plays an important role in cell proliferation and NF-κB signaling pathway.