β-Catenin is O-GlcNAc glycosylated at Serine 23: Implications for β-catenin's subcellular localization and transactivator function

被引：43

作者：

Ha, Jacqueline R. ^{[1
]}

Hao, Li ^{[1
]}

Venkateswaran, Geetha ^{[1
]}

Huang, Yu Hao ^{[1
]}

Garcia, Elizabeth ^{[1
]}

Persad, Sujata ^{[1
]}

机构：

[1] Univ Alberta, Fac Med & Dent, Dept Pediat, Edmonton, AB T6G 2E1, Canada

来源：

EXPERIMENTAL CELL RESEARCH | 2014年 / 321卷 / 02期

关键词：

beta-Catenin; O-GlcNAcylation; Subcellular localization; Transcriptional function; SCANNING MUTAGENESIS; COLON-CARCINOMA; CYCLIN D1; TARGET; ACTIVATION; NUCLEAR; ROLES; PHOSPHORYLATION; IDENTIFICATION; EXPRESSION;

D O I：

10.1016/j.yexcr.2013.11.021

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: We have previously reported that beta-catenin is post-translationally modified with a single O-linked attachment of beta-N-acetyl-glucosamine (O-GlcNAc). We showed that O-GlcNAc regulated beta-catenin's subcellular localization and transcriptional activity. Objective: The objectives of this investigation were to identify the putative O-GlcNAc sites of beta-catenin and the relevance of identified sites in the regulation of beta-catenin's localization and transcriptional activity. Method: Missense mutations were introduced to potential O-GlcNAc sites of pEGFP-C2-N-Terminal- or pEGFP-C2-Wild Type-beta-catenin by site-directed mutagenesis. We determined the levels of O-GlcNAc-beta-catenin, subcellular localization, interaction with binding partners and transcriptional activity of the various constructs. Results: Serine 23 of beta-catenin was determined as a site for O-GlcNAc modification which regulated its subcellular distribution, its interactions with cellular partners and consequently its transcriptional activity. Significance: O-GlcNAcylation of Serine 23 is a novel regulatory modification for beta-catenin's subcellular localization and transcriptional activity. This study is the first report to characterize site specific regulation of beta-catenin by the O-GlcNAc modification. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：153 / 166

页数：14

共 29 条

[1] beta-catenin is a target for the ubiquitin-proteasome pathway [J].

Aberle, H ;

Bauer, A ;

Stappert, J ;

Kispert, A ;

Kemler, R .

EMBO JOURNAL, 1997, 16 (13) :3797-3804

[2] Essential role of BCL9-2 in the switch between β-catenin's adhesive and transcriptional functions [J].

Brembeck, FH ;

Schwarz-Romond, T ;

Bakkers, J ;

Wilhelm, S ;

Hammerschmidt, M ;

Birchmeier, W .

GENES & DEVELOPMENT, 2004, 18 (18) :2225-2230

[3] RETRACTED: Evidence that Armadillo transduces Wingless by mediating nuclear export or cytosolic activation of Pangolin (Retracted Article. See vol 116, pg 481, 2004) [J].

Chan, SK ;

Struhl, G .

CELL, 2002, 111 (02) :265-280

[4] β-Catenin signaling in prostate cancer:: an early perspective [J].

Chesire, DR ;

Isaacs, WB .

[5]

CHOU CF, 1992, J BIOL CHEM, V267, P3901

[6] Wnt/β-catenin signaling in development and disease [J].

Clevers, Hans .

CELL, 2006, 127 (03) :469-480

[7] The metalloproteinase matrilysin is a target of β-catenin transactivation in intestinal tumors [J].

Crawford, HC ;

Fingleton, BM ;

Rudolph-Owen, LA ;

Goss, KJH ;

Rubinfeld, B ;

Polakis, P ;

Matrisian, LM .

ONCOGENE, 1999, 18 (18) :2883-2891

[8] HIGH-RESOLUTION EPITOPE MAPPING OF HGH-RECEPTOR INTERACTIONS BY ALANINE-SCANNING MUTAGENESIS [J].

CUNNINGHAM, BC ;

WELLS, JA .

SCIENCE, 1989, 244 (4908) :1081-1085

[9] Phospho-regulation of β-catenin adhesion and signaling functions [J].

Daugherty, Rebecca Leadem ;

Gottardi, Cara J. .

PHYSIOLOGY, 2007, 22 (05) :303-309

[10] Cycling of O-linked β-N-acetylglucosamine on nucleocytoplasmic proteins [J].

Hart, Gerald W. ;

Housley, Michael P. ;

Slawson, Chad .

NATURE, 2007, 446 (7139) :1017-1022

← 1 2 3 →