구.추천논문, 상위피인용논문
- 조회2,494
Sungho Moon1,†, Wantae Kim1,†, Soyoung Kim1, Youngeun Kim1, Yonghee Song1, Oleksii Bilousov2, Jiyoung Kim1, Taebok Lee1, Boksik Cha1, Minseong Kim1, Hanjun Kim1, Vladimir L Katanaev*,2,3 and Eek-hoon Jho*,1
1Department of Life Science, University of Seoul, Seoul, Korea
2Department of Pharmacology and Toxicology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
3School of Biomedicine, Far Eastern Federal University, Vladivostok, Russian Federation
* Corresponding author : Vladimir L Katanaev, Eek-hoon Jho
† These authors contributed equally to this work
Abstract
Hippo signaling controls organ size by regulating cell proliferation and apoptosis. Yes?associated protein (YAP) is a key downstream effector of Hippo signaling, and LATS?mediated phosphorylation of YAP at Ser127 inhibits its nuclear localization and transcriptional activity. Here, we report that Nemo?like kinase (NLK) phosphorylates YAP at Ser128 both in vitro and in vivo, which blocks interaction with 14?3?3 and enhances its nuclear localization. Depletion of NLK increases YAP phosphorylation at Ser127 and reduces YAP?mediated reporter activity. These results suggest that YAP phosphorylation at Ser128 and at Ser127 may be mutually exclusive. We also find that with the increase in cell density, nuclear localization and the level of NLK are reduced, resulting in reduction in YAP phosphorylation at Ser128. Furthermore, knockdown of Nemo (the Drosophila NLK) in fruit fly wing imaginal discs results in reduced expression of the Yorkie (the Drosophila YAP) target genes expanded and DIAP1, while Nemo overexpression reciprocally increased the expression. Overall, our data suggest that NLK/Nemo acts as an endogenous regulator of Hippo signaling by controlling nuclear localization and activity of YAP/Yorkie.
논문정보
- Research article
- 2017년 01월 (BRIC 등록일 2017-02-20)
- 국내(교신)+국외 연구진
- 생명과학 > 분자생물학
- 120회 이상 인용된 논문 (상위피인용논문 등록일 2022-11-04)
- 구・추천논문
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