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XB-ART-50749
Dev Cell June 22, 2015; 33 (6): 660-74.

Kdm2a/b Lysine Demethylases Regulate Canonical Wnt Signaling by Modulating the Stability of Nuclear β-Catenin.

Lu L , Gao Y , Zhang Z , Cao Q , Zhang X , Zou J , Cao Y .


Abstract
In the absence of Wnt activation, cytosolic β-catenin is degraded through GSK3/CK1-mediated phosphorylation at the N terminus. Here, we show that, upon Wnt activation, the stability of nuclear β-catenin is regulated via methylation/demethylation. The protein lysine demethylases Kdm2a and Kdm2b regulate the turnover of non-phosphorylated β-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 β-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 β-catenin, concurrent with the upregulation of β-catenin target genes. This mechanism is required for controlling the output of the Wnt/β-catenin signaling pathway to maintain normal cellular functions.

PubMed ID: 26004508
Article link: Dev Cell

Genes referenced: actl6a ag1 bmp4 c11orf96 chrd.1 csnk1a1 ctnnb1 ctrl gapdh gnl3 hoxb9 hoxc9-like kdm2a kdm2b krt12.4 krt8.1 myl2 nodal3.1 nodal3.2 otx2 sia1 tcf7l1 ventx1.1 ventx1.2 ventx2.2 wnt3a wnt8a
Morpholinos: kdm2a MO1 kdm2b MO1


Article Images: [+] show captions
References:
Fagotto, 2015, Pubmed


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