AACR 2014 --Lianhua Piao

Abstract Number: 377
Presentation Title: SMYD2-dependent PARP1 methylation promotes Poly(ADP-ribosyl)ation activity in cancer cells
Presentation Time: Sunday, Apr 06, 2014, 1:00 PM - 5:00 PM
Location: Hall A-E, Poster Section 17
Poster Board Number: 5
Author Block: Lianhua Piao, Yusuke Nakamura, Ryuji Hamamoto. Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL
Abstract Body: Poly(ADP-ribose) polymerase-1 (PARP1) catalyzes the poly(ADP-ribosyl)ation of protein acceptors using NAD+ as the substrate is now considered as an important target for development of anticancer therapy. PARP1 is known to be posttranslationally modified in various ways including phosphorylation and ubiquitination, but the physiological role of PARP1 methylation is not well understood. Here we demonstrated that the histone methyltransferase SMYD2 (SET and MYND domain containing 2), which plays critical roles in human carcinogenesis, mono-methylated PARP1. We found lysine 528 to be a target of SMYD2-dependent PARP1 methylationa and that an N-Terminal DNA binding domain of PARP1 interact with an N-terminal domain of SMYD2. Importantly, methylated PARP1 revealed enhanced poly(ADP-ribose) formation after oxidative stress, and positively regulated the poly(ADP-ribosyl)ation activity of PARP1. Hence, our study unveils a novel mechanism of PARP1 in human cancer through its methylation by SMYD2.