Critical roles of SMYD2-mediated β-catenin methylation for nuclear translocation and activation of Wnt signaling

By Xiaolan Deng, Ryuji Hamamoto, T. Vougiouklakis, Rui Wang, Yuichiro Yoshioka, Takehiro Suzuki, N. Dohmae, Y. Matsuo, Jae-Hyun Park, Yusuke Nakamura. 2017

43 citations recorded by the source corpus.

Accumulation of β-catenin in the nucleus is a hallmark of activation of the Wnt/β-catenin signaling pathway, which drives development of a large proportion of human cancers. However, the mechanism of β-catenin nuclear translocation has not been well investigated. Here we report biological significance of SMYD2-mediated lysine 133 (K133) methylation of β-catenin on its nuclear translocation. Knockdown of SMYD2 attenuates the nuclear localization of β-catenin protein in human cancer cells. Consequently, transcriptional levels of well-known Wnt-signaling molecules, cMYC and CCND1, are significantly reduced. Substitution of lysine 133 to alanine in β-catenin almost completely abolishes its nuclear localization. We also demonstrate the K133 methylation is critical for the interaction of β-catenin with FOXM1. Furthermore, after treatment with a SMYD2 inhibitor, significant reduction of nuclear β-catenin and subsequent induction of cancer cell death are observed. Accordingly, our results imply that β-catenin methylation by SMYD2 promotes its nuclear translocation and activation of Wnt signaling.

Subfields: Molecular Biology

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In Molecular Biology

1. Syuzo Kaneko
2. Ryuji Hamamoto
3. Yusuke Nakamura
4. N. Dohmae
5. Takehiro Suzuki
6. Makoto Nakakido

Citations in the corpus

• The histone methyltransferase SMYD2 is a novel therapeutic target for the induction of apoptosis in ovarian clear cell carcinoma cells (2020, background): “Additionally, previous studies have highlighted the role of SMYD2 in the regulation of cancer cell growth (13,17).”