Abstract 4487: A critical role of PARylation in regulating the functions of OVOL2

Abstract

Abstract Poly(ADP-ribosyl)ation (PARylation) is one of the post-translational modifications, by which the ADP-ribose (PAR) polymers are added to the specific protein by a PAR polymerase (PARP). In the about 50 years' studies, this specific modification has been verified to be related to multiple important biological functions including cell death, cell differentiation, histone modification, transcriptional regulation, DNA repair and genome stability. Ovo-like 2 (OVOL2), a novel zinc finger transcriptional factor, contains a Snail/Gli (SNAG) motif at the N-terminal to possess a transcriptional regulatory activity and four DNA-binding Cys2-His2 (C2H2) zinc finger domains at the C-terminal to bind with DNA. OVOL2 is demonstrated to be involved in the cranial neural tube, angiogenesis, heart and placental development. In addition, OVOL2 can also suppress cell cycle and terminate differentiation of keratinocyte by directly inhibiting of c-Myc and Notch1. However, the regulation and biological function of OVOL2 are still largely unknown. In this study, we identify the binding targets, PARP1 and NPM1, of OVOL2. In addition, we report that the function of OVOL2 is regulated by PARP1 through PARylation, which modifies on C2H2 zinc finger domains and plays an important role in the regulation of OVOL2 functions. PARylated OVOL2, but not the 3K mutant, alters focal adhesion and cell cycle, resulting in the formation of polyploidy in cells. Our findings not only have significant implications for the cellular functions of OVOL2, but also provide a better understanding on the multiple biological functions of the PARylation. Citation Format: Rui Zhang, Boan Li, Yih-Cherng Liou. A critical role of PARylation in regulating the functions of OVOL2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4487. doi:10.1158/1538-7445.AM2017-4487