期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1863, 期 4, 页码 1013-1022出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2017.01.028
关键词
beta-catenin; Dephosphorylation; Germ cell development; NLK; Wip1
资金
- National Research Foundation of Korea (NRF) - Korea government (MSIP) [2009-0093822, 2011-0030043, 2016R1D1A1A02937487]
- National Research Foundation of Korea [2009-0093822, 2016R1D1A1A02937487] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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 beta-catenin. Additionally, WIP1 depletion impaired germ cell development, as evidenced by the expression of Oct4 and the germ cell-specific markers Ddx4, Nanos3 and Dndl 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 (Soxl 7), a downstream target of Wnt. These results indicate that WIP1 is essential for germ cell development, which is known to require Wnt activity. (C) 2017 Elsevier B.V. All rights reserved.
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