The histone methyltransferase SMYD2 methylates PARP1 and promotes poly(ADP-ribosyl)ation activity in cancer cells.
By Lianhua Piao, Daechun Kang, Takehiro Suzuki, A. Masuda, N. Dohmae, Yusuke Nakamura, Ryuji Hamamoto. 2014
104 citations recorded by the source corpus.
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.
Subfields: Molecular Biology, Oncology
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In Molecular Biology
- Ryuji Hamamoto
- Yusuke Nakamura
- Takehiro Suzuki
- N. Dohmae
- Makoto Nakakido
- Lianhua Piao
- Yuichiro Yoshioka
- Zhenzhong Deng
In Oncology
Citations in the corpus
- Dysregulation of AKT Pathway by SMYD2-Mediated Lysine Methylation on PTEN (2015, unknown): “Our present and previous studies demonstrated that SMYD2 is mainly localized in the cytoplasm (Figure 2A) [21,29,42], implying that the functionally important substrates of SMYD2 in human tumorigenesis may not be histone proteins but non-histone cytoplasmic proteins.”
- PRMT1 promotes mitosis of cancer cells through arginine methylation of INCENP (2015, methodology): “In vitro methyltransferase assays were described previously [37, 39-46].”
- Critical roles of SMYD2-mediated β-catenin methylation for nuclear translocation and activation of Wnt signaling (2017, background): “Our group has reported critical roles of SMYD2-mediated methylation in tumorigenesis as a methyltransferase [6-9].”
- PRMT6 increases cytoplasmic localization of p21CDKN1A in cancer cells through arginine methylation and makes more resistant to cytotoxic agents (2015, background): “Even though whether PRMT6 methylates p21 in the nucleus or in the cytoplasm is still unknown, the present results imply that PRMT6 may play an important role in the functional regulation of not only histone proteins but also non-histone proteins as other histone methyltransferases [28–34].”
- SMYD3-mediated lysine methylation in the PH domain is critical for activation of AKT1 (2016, unknown): “Leica confocal microscopy (SP5 Tandem Scanner Spectral 2-Photon Confocal) was used for observation of stained cells [54].”