alpha-catenin SUMOylation increases I kappa B alpha stability and inhibits breast cancer progression

作者：Chen, Huan; Xu, Zhaowei; Li, Xiahui; Yang, Yangyang; Li, Bowen; Li, Yanan; Xia, Kangkai; Wang, Jian; Li, Shujing; Wang, Miao^*; Wu, Huijian^*

来源：Oncogenesis, 2018, 7(3): 28.

DOI：10.1038/s41389-018-0037-7

• TUMOR-SUPPRESSOR
• INTERCELLULAR-ADHESION
• ADHERENS JUNCTIONS
• TARGET GENES
• UBIQUITIN
• SUMO
• TRANSCRIPTION
• ACTIVATION
• EXPRESSION
• CARCINOMA

alpha-catenin has been demonstrated to suppress several different types of cancers. Here we demonstrate that a-catenin is modified by SUMO protein, which covalently binds a-catenin at the carboxy terminus at lysine 870. Substitution of lysine 870 with arginine completely abolishes alpha-catenin SUMOylation. This modification can be removed by SENP1. However, alpha-catenin SUMOylation does not affect its stability and subcellular localization. In addition, we observed that the SUMOylation-deficient alpha-catenin mutant has a reduced interaction with I kappa B alpha which prevents subsequent ubiquitination of I kappa B alpha, and therefore a reduced suppression of expression of the NF-kappa B target genes TNF-alpha, IL-8, VEGF, and uPA. In addition, the alpha-catenin SUMOylation mutant shows impaired suppression of tumor growth. These results demonstrate that SUMOylation at lysine 870 of alpha-catenin plays a key role in the suppression of the NF-kappa B pathway, which inhibits breast cancer tumor growth and migration.

• 出版日期2018-3
• 单位大连理工大学