期刊
DEVELOPMENTAL CELL
卷 33, 期 6, 页码 660-674出版社
CELL PRESS
DOI: 10.1016/j.devcel.2015.04.006
关键词
-
资金
- Ministry of Science and Technology [2011CB943804, 2014CB964701]
- National Science Foundation of China [31271544, 31261160492]
In the absence of Wnt activation, cytosolic beta-catenin is degraded through GSK3/CK1-mediated phosphorylation at the N terminus. Here, we show that, upon Wnt activation, the stability of nuclear beta-catenin is regulated via methylation/demethylation. The protein lysine demethylases Kdm2a and Kdm2b regulate the turnover of non-phosphorylated beta-catenin specifically within the nucleus via direct interaction with the fourth and fifth armadillo repeats. The lysine residues within this region are required for the methylation of non-phosphorylated beta-catenin, which is demethylated by Kdm2a/b and subsequently ubiquitylated. During Xenopus embryogenesis, kdm2a/b genes are transcribed during early embryogenesis and are required for the specification of the body axis. Kdm2a/b knockdown in Xenopus embryos leads to increases in non-phosphorylated and methylated beta-catenin, concurrent with the upregulation of beta-catenin target genes. This mechanism is required for controlling the output of the Wnt/beta-catenin signaling pathway to maintain normal cellular functions.
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