WIKI4, a Novel Inhibitor of Tankyrase and Wnt/β-Catenin Signaling

被引：78

作者：

James, Richard G. ^{[1
,2
,5
]}

Davidson, Kathryn C. ^{[1
,2
,3
,5
]}

Bosch, Katherine A. ^{[1
,2
,3
,5
]}

Biechele, Travis L. ^{[1
,2
,3
,5
]}

Robin, Nicholas C. ^{[1
,2
,3
,5
]}

Taylor, Russell J. ^{[1
,2
,5
]}

Major, Michael B. ^{[6
]}

Camp, Nathan D. ^{[1
,2
,3
,5
]}

Fowler, Kerry ^{[7
]}

Martins, Timothy J. ^{[2
,4
,5
]}

Moon, Randall T. ^{[1
,2
,3
,5
]}

机构：

[1] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA

[2] Inst Stem Cell & Regenerat Med, Seattle, WA USA

[3] Howard Hughes Med Inst, Seattle, WA USA

[4] Quellos High Throughput Screening Core, Seattle, WA USA

[5] Univ Washington, Sch Med, Seattle, WA USA

[6] Univ North Carolina Chapel Hill, Dept Cell & Dev Biol, Chapel Hill, NC USA

[7] KWF Consulting, Seattle, WA USA

来源：

PLOS ONE | 2012年 / 7卷 / 12期

基金：

美国国家卫生研究院;

关键词：

EMBRYONIC STEM-CELLS; BETA-CATENIN; SULFATE PROTEOGLYCAN; MOUSE DEVELOPMENT; PATHWAY; ACTIVATION; DIFFERENTIATION; REGENERATION; REQUIREMENT; GROWTH;

D O I：

10.1371/journal.pone.0050457

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The Wnt/beta-catenin signaling pathway controls important cellular events during development and often contributes to disease when dysregulated. Using high throughput screening we have identified a new small molecule inhibitor of Wnt/beta-catenin signaling, WIKI4. WIKI4 inhibits expression of beta-catenin target genes and cellular responses to Wnt/beta-catenin signaling in cancer cell lines as well as in human embryonic stem cells. Furthermore, we demonstrate that WIKI4 mediates its effects on Wnt/beta-catenin signaling by inhibiting the enzymatic activity of TNKS2, a regulator of AXIN ubiquitylation and degradation. While TNKS has previously been shown to be the target of small molecule inhibitors of Wnt/beta-catenin signaling, WIKI4 is structurally distinct from previously identified TNKS inhibitors.

引用

页数：10

共 49 条

[11] Wnt/β-catenin signaling promotes differentiation, not self-renewal, of human embryonic stem cells and is repressed by Oct4 [J].

Davidson, Kathryn C. ;

Adams, Allison M. ;

Goodson, Jamie M. ;

McDonald, Circe E. ;

Potter, Jennifer C. ;

Berndt, Jason D. ;

Biechele, Travis L. ;

Taylor, Russell J. ;

Moon, Randall T. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (12) :4485-4490

[12]

de La Coste A, 1998, P NATL ACAD SCI USA, V95, P8847

[13] Illegitimate WNT signaling promotes proliferation of multiple myeloma cells [J].

Derksen, PWB ;

Tjin, E ;

Meijer, HP ;

Klok, MD ;

Mac Gillavry, HD ;

van Oers, MHJ ;

Lokhorst, HM ;

Bloem, AC ;

Clevers, H ;

Nusse, R ;

van der Neut, R ;

Spaargaren, M ;

Pals, ST .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (16) :6122-6127

[14] A transgenic Lef1/β-catenin-dependent reporter is expressed in spatially restricted domains throughout zebrafish development [J].

Dorsky, RI ;

Sheldahl, LC ;

Moon, RT .

DEVELOPMENTAL BIOLOGY, 2002, 241 (02) :229-237

[15] Aurora kinase A is a target of Wnt/β-catenin involved in multiple myeloma disease progression [J].

Dutta-Simmons, Jui ;

Zhang, Yunyu ;

Gorgun, Gullu ;

Gatt, Moshe ;

Mani, Mala ;

Hideshima, Teru ;

Takada, Kohichi ;

Carlson, Nicole E. ;

Carrasco, Daniel E. ;

Tai, Yu-Tzu ;

Raje, Noopur ;

Letai, Anthony G. ;

Anderson, Kenneth C. ;

Carrasco, Daniel R. .

BLOOD, 2009, 114 (13) :2699-2708

[16] High expression and nuclear localization of β-catenin in diffuse large B-cell lymphoma [J].

Ge, Xueling ;

Lv, Xiao ;

Feng, Lili ;

Liu, Xiaoqian ;

Wang, Xin .

MOLECULAR MEDICINE REPORTS, 2012, 5 (06) :1433-1437

[17] Constitutive activation of the Wnt canonical pathway in mantle cell lymphoma [J].

Gelebart, Pascal ;

Anand, Mona ;

Armanious, Hanan ;

Peters, Anthea C. ;

Bard, Jennifer Dien ;

Amin, Hesham M. ;

Lai, Raymond .

BLOOD, 2008, 112 (13) :5171-5179

[18]

HAEGEL H, 1995, DEVELOPMENT, V121, P3529

[19] Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling [J].

Huang, Shih-Min A. ;

Mishina, Yuji M. ;

Liu, Shanming ;

Cheung, Atwood ;

Stegmeier, Frank ;

Michaud, Gregory A. ;

Charlat, Olga ;

Wiellette, Elizabeth ;

Zhang, Yue ;

Wiessner, Stephanie ;

Hild, Marc ;

Shi, Xiaoying ;

Wilson, Christopher J. ;

Mickanin, Craig ;

Myer, Vic ;

Fazal, Aleem ;

Tomlinson, Ronald ;

Serluca, Fabrizio ;

Shao, Wenlin ;

Cheng, Hong ;

Shultz, Michael ;

Rau, Christina ;

Schirle, Markus ;

Schlegl, Judith ;

Ghidelli, Sonja ;

Fawell, Stephen ;

Lu, Chris ;

Curtis, Daniel ;

Kirschner, Marc W. ;

Lengauer, Christoph ;

Finan, Peter M. ;

Tallarico, John A. ;

Bouwmeester, Tewis ;

Porter, Jeffery A. ;

Bauer, Andreas ;

Cong, Feng .

NATURE, 2009, 461 (7264) :614-620

[20] Requirement for β-catenin in anterior-posterior axis formation in mice [J].

Huelsken, J ;

Vogel, R ;

Brinkmann, V ;

Erdmann, B ;

Birchmeier, C ;

Birchmeier, W .

JOURNAL OF CELL BIOLOGY, 2000, 148 (03) :567-578

← 1 2 3 4 5 →