Wip1 directly dephosphorylates NLK and increases Wnt activity during germ cell development

Seung Ju Cho, Bok Sik Cha, Ok Seon Kwon, Jisun Lim, Dong Myung Shin, Dong Wook Han, Tohru Ishitani, Eek hoon Jho, Albert J. Fornace, Hyuk Jin Cha

研究成果: Contribution to journalArticle査読

7 被引用数 (Scopus)

抄録

Mice null for wild-type p53-induced phosphatase 1 (WIP1) display defects in testis development and spermatogenesis, resulting in reduced fertility. However, the molecular mechanism underlying these abnormalities in the testis remains uncharacterized. We report that the phosphatase activity of WIP1 increases Wnt activity through Nemo-like kinase (NLK). WIP1 directly interacted with NLK, which is highly homologous to p38 MAPK, a WIP1 substrate, and dephosphorylated its activation site. The WIP1-mediated inhibition of NLK activity markedly decreased the phosphorylation of lymphoid enhancer-binding factor 1 (LEF1), enhancing its interaction with β-catenin. Additionally, WIP1 depletion impaired germ cell development, as evidenced by the expression of Oct4 and the germ cell-specific markers Ddx4, Nanos3 and Dnd1 during the development of germ cells from Oct4-GFP transgenic (OG2) mouse embryonic stem cells (mESCs). The expression of WIP1, whose level was significantly lower after the differentiation of germ cells from mESCs, occurred in parallel with the expression of germ cell development markers and SRY-box 17 (Sox17), a downstream target of Wnt. These results indicate that WIP1 is essential for germ cell development, which is known to require Wnt activity.

本文言語英語
ページ(範囲)1013-1022
ページ数10
ジャーナルBiochimica et Biophysica Acta - Molecular Basis of Disease
1863
4
DOI
出版ステータス出版済み - 4 1 2017
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子医療
  • 分子生物学

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