| Literature DB >> 24726141 |
Lianhua Piao1, Daechun Kang2, Takehiro Suzuki3, Akiko Masuda3, Naoshi Dohmae3, Yusuke Nakamura1, Ryuji Hamamoto4.
Abstract
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 post-translationally modified in various ways including phosphorylation and ubiquitination, but the physiological role of PARP1 methylation is not well understood. Herein we demonstrated that the histone methyltransferase SMYD2, which plays critical roles in human carcinogenesis, mono-methylated PARP1. We confirmed lysine 528 to be a target of SMYD2-dependent PARP1 methylation by LC-MS/MS and Edman Degradation analyses. 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.Entities:
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Year: 2014 PMID： 24726141 PMCID： PMC4094795 DOI： 10.1016/j.neo.2014.03.002
Source DB: PubMed Journal: Neoplasia ISSN： 1476-5586 Impact factor: 5.715