Abstract 5087: Peli 1 targets BubR1 for ubiquitinational degradation and induces aneuploidy transformation

Abstract

Abstract Disruption of the BubR1-mediated function negatively impacts mitotic checkpoint control, increases chromosomal instability, and is associated with infertility, life span and cancer. Therefore, BubR1 plays an important role in preventing abnormal mitotic cells with chromosomal aneuploidy from achieving neoplastic aneuploidy, however it remains unclear how the signalling activates or inactivates the BubR1 function during the neoplastic transformation. Here, we report that Peli 1, a new family of signal-responsive E3 ubiquitin ligase, directly interacts with BubR1. This interaction promotes the ubiquitin-mediated degradation, and prevents the kinetochore association of BubR1. In addition, cells expressing Peli 1 led to severe mitotic defects and displayed severe chromosomal aneuploidy in vitro and in vivo. Together, these results suggest that Peli 1 expression acts as a potent causative signalling against chromosome integrity by mediating the ubiquitinational degradation of BubR1, and thus contributes to the development of neoplastic chromosome aneuploidy. Citation Format: Suhyeon Kim, Hye-Young Park, Ha Rim Song, Heounjeong Go, Hyeseong Cho, Doo Hyun Chung, Chang-Woo Lee. Peli 1 targets BubR1 for ubiquitinational degradation and induces aneuploidy transformation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5087. doi:10.1158/1538-7445.AM2014-5087