Yap1 Acts Downstream of α-Catenin to Control Epidermal Proliferation

被引：905

作者：

Schlegelmilch, Karin ^{[1
,2
,3
,4
]}

Mohseni, Morvarid ^{[1
,2
,3
]}

Kirak, Oktay ^{[5
]}

Pruszak, Jan ^{[3
,5
]}

Rodriguez, J. Renato ^{[5
]}

Zhou, Dawang ^{[6
]}

Kreger, Bridget T. ^{[7
]}

Vasioukhin, Valera ^{[7
]}

Avruch, Joseph ^{[6
]}

Brummelkamp, Thijn R. ^{[5
]}

Camargo, Fernando D. ^{[1
,2
,3
]}

机构：

[1] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA

[2] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[3] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[4] FU Berlin, Inst Chem Biochem, D-14195 Berlin, Germany

[5] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[6] Massachusetts Gen Hosp, Dept Mol & Cellular Biol, Boston, MA 02114 USA

[7] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA

来源：

CELL | 2011年 / 144卷 / 05期

关键词：

ORGAN SIZE CONTROL; TUMOR-SUPPRESSOR; CELL-PROLIFERATION; PROMOTES APOPTOSIS; SIGNALING PATHWAY; HIPPO PATHWAY; PROGENITOR CELLS; TEAD/TEF FAMILY; PROTEIN-KINASE; GROWTH-CONTROL;

D O I：

10.1016/j.cell.2011.02.031

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

During development and regeneration, proliferation of tissue-specific stem cells is tightly controlled to produce organs of a predetermined size. The molecular determinants of this process remain poorly understood. Here, we investigate the function of Yap1, the transcriptional effector of the Hippo signaling pathway, in skin biology. Using gain- and loss-of-function studies, we show that Yap1 is a critical modulator of epidermal stem cell proliferation and tissue expansion. Yap1 mediates this effect through interaction with TEAD transcription factors. Additionally, our studies reveal that alpha-catenin, a molecule previously implicated in tumor suppression and cell density sensing in the skin, is an upstream negative regulator of Yap1. alpha-catenin controls Yap1 activity and phosphorylation by modulating its interaction with 14-3-3 and the PP2A phosphatase. Together, these data identify Yap1 as a determinant of the proliferative capacity of epidermal stem cells and as an important effector of a "crowd control" molecular circuitry in mammalian skin.

引用

页码：782 / 795

页数：14

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