Release Time:2019-03-12  Hits:

Indexed by: Journal Article

Date of Publication: 2018-01-01

Journal: Oncogenesis

Included Journals: SCIE

Volume: 7

Issue: 3

ISSN: 2157-9024

Abstract: alpha-catenin has been demonstrated to suppress several different types of cancers. Here we demonstrate that alpha-catenin is modified by SUMO protein, which covalently binds alpha-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 IkappaBalpha which prevents subsequent ubiquitination of IkappaBalpha, and therefore a reduced suppression of expression of the NF-kappaB 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-kappaB pathway, which inhibits breast cancer tumor growth and migration.