Inhibition of Wnt signaling by Dishevelled PDZ peptides

被引：134

作者：

Zhang, Yingnan ^{[1
]}

Appleton, Brent A. ^{[1
]}

Wiesmann, Christian ^{[1
]}

Lau, Ted ^{[2
]}

Costa, Mike ^{[2
]}

Hannoush, Rami N. ^{[1
]}

Sidhu, Sachdev S. ^{[1
]}

机构：

[1] Genentech Inc, Dept Prot Engn, San Francisco, CA 94080 USA

[2] Genentech Inc, Dept Canc Targets & Pathways, San Francisco, CA 94080 USA

来源：

NATURE CHEMICAL BIOLOGY | 2009年 / 5卷 / 04期

关键词：

BETA-CATENIN; TRANSCRIPTIONAL ACTIVITY; DOMAIN; SPECIFICITY; PATHWAY; OVEREXPRESSION; ANTAGONIST; ACTIVATION; PROTEINS; CANCER;

D O I：

10.1038/nchembio.152

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：

Dishevelled proteins are key regulators of Wnt signaling pathways that have been implicated in the progression of human cancers. We found that the binding cleft of the Dishevelled PDZ domain is more flexible than those of canonical PDZ domains and enables recognition of both C-terminal and internal peptides. These peptide ligands inhibit Wnt/beta-catenin signaling in cells, showing that Dishevelled PDZ domains are potential targets for small-molecule cancer therapeutics.

引用

页码：217 / 219

页数：3

共 19 条

[1]

Abramoff M. D., 2004, BIOPHOTONICS INT, V11, P36, DOI DOI 10.1201/9781420005615.AX4

[2] Comparative structural analysis of the Erbin PDZ domain and the first PDZ domain of ZO-1 - Insights into determinants of PDZ domain specificity [J].

Appleton, Brent A. ;

Zhang, Yingnan ;

Wu, Ping ;

Yin, Jian Ping ;

Hunziker, Walter ;

Skelton, Nicholas J. ;

Sidhu, Sachdev S. ;

Wiesmann, Christian .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (31) :22312-22320

[3] Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways [J].

Axelrod, JD ;

Miller, JR ;

Shulman, JM ;

Moon, RT ;

Perrimon, N .

GENES & DEVELOPMENT, 1998, 12 (16) :2610-2622

[4] Trojan peptides: the penetratin system for intracellular delivery [J].

Derossi, D ;

Chassaing, G ;

Prochiantz, A .

TRENDS IN CELL BIOLOGY, 1998, 8 (02) :84-87

[5] An antagonist of dishevelled protein-protein interaction suppresses β-catenin-dependent tumor cell growth [J].

Fujii, Naoaki ;

You, Liang ;

Xu, Zhidong ;

Uematsu, Kazutsugu ;

Shan, Jufang ;

He, Biao ;

Mikami, Iwao ;

Edmondson, Lillian R. ;

Neale, Geoffrey ;

Zheng, Jie ;

Guy, R. Kiplin ;

Jablons, David M. .

CANCER RESEARCH, 2007, 67 (02) :573-579

[6] Dishevelled proteins lead to two signaling pathways - Regulation of LEF-1 and c-Jun N-terminal kinase in mammalian cells [J].

Li, L ;

Yuan, HD ;

Xie, W ;

Mao, JH ;

Caruso, AM ;

McMahon, A ;

Sussman, DJ ;

Wu, DQ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (01) :129-134

[7] Indole-2-amide based biochemical antagonist of Dishevelled PDZ domain interaction down-regulates Dishevelled-driven Tcf transcriptional activity [J].

Mahindroo, Neeraj ;

Punchihewa, Chandanamall ;

Bail, Allison M. ;

Fujii, Naoaki .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (03) :946-949

[8] The many ways of Wnt in cancer [J].

Polakis, Paul .

CURRENT OPINION IN GENETICS & DEVELOPMENT, 2007, 17 (01) :45-51

[9] Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis [J].

Rothbächer, U ;

Laurent, MN ;

Deardorff, MA ;

Klein, PS ;

Cho, KWY ;

Fraser, SE .

EMBO JOURNAL, 2000, 19 (05) :1010-1022

[10] Identification of a specific inhibitor of the dishevelled PDZ domain [J].

Shan, JF ;

Shi, DL ;

Wang, JM ;

Zheng, J .

BIOCHEMISTRY, 2005, 44 (47) :15495-15503

← 1 2 →