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Titolo:
Membrane-anchored plakoglobins have multiple mechanisms of action in Wnt signaling
Autore:
Klymkowsky, MW; Williams, BO; Barish, GD; Varmus, HE; Vourgourakis, YE;
Indirizzi:
Univ Colorado, Boulder, CO 80309 USA Univ Colorado Boulder CO USA 80309Univ Colorado, Boulder, CO 80309 USA NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA
Titolo Testata:
MOLECULAR BIOLOGY OF THE CELL
fascicolo: 10, volume: 10, anno: 1999,
pagine: 3151 - 3169
SICI:
1059-1524(199910)10:10<3151:MPHMMO>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADENOMATOUS POLYPOSIS-COLI; BETA-CATENIN GENE; GLYCOGEN-SYNTHASE KINASE-3; TRANSCRIPTION FACTOR LEF-1; TUMOR-SUPPRESSOR PROTEIN; EARLY XENOPUS-EMBRYOS; AXIS FORMATION; HEPATOCELLULAR CARCINOMAS; FUNCTIONAL INTERACTION; NUCLEAR-LOCALIZATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
96
Recensione:
Indirizzi per estratti:
Indirizzo: Klymkowsky, MW Univ Colorado, Boulder, CO 80309 USA Univ Colorado BoulderCO USA 80309 , Boulder, CO 80309 USA
Citazione:
M.W. Klymkowsky et al., "Membrane-anchored plakoglobins have multiple mechanisms of action in Wnt signaling", MOL BIOL CE, 10(10), 1999, pp. 3151-3169

Abstract

In Wnt signaling, beta-catenin and plakoglobin transduce signals to the nucleus through interactions with TCF-type transcription factors. However, when plakoglobin is artificially engineered to restrict it to the cytoplasm by fusion with the transmembrane domain of connexin (cnxPg), it efficiently induces a Wnt-like axis duplication phenotype in Xenopus. Ln Xenopus embryos, maternal XTCF3 normally represses ventral expression of the dorsalizing gene Siamois. Two models have been proposed to explain the Wnt-like activity of cnxPg: 1) that cnxPg inhibits the machinery involved in the turnover of cytosolic beta-catenin, which then accumulates and inhibits maternal XTCF3, and 2) that cnxPg directly acts to inhibit XTCF3 activity. To distinguish between these models, we created a series of N-terminal deletion mutations of cnxPg and examined their ability to induce an ectopic axis in Xenopus,activate a TCF-responsive reporter (OT), stabilize beta-catenin, and colocalize with components of the Wnt signaling pathway. cnxPg does not colocalize with the Wnt pathway component Dishevelled, but it does lead to the redistribution of APC and Axin, two proteins involved in the regulation of beta-catenin turnover. Expression of cnxPg increases levels of cytosolic beta-catenin; however, this effect does not completely explain its signaling activity. Although cnxPg and Wnt-1 stabilize beta-catenin to similar extents, cnxPg activates OT to 10- to 20-fold higher levels than Wnt-1. Moreover, although LEF1 and TCF4 synergize with beta-catenin and plakoglobin to activateOT, both suppress the signaling activity of cnxPg. In contrast, XTCF3 suppresses the signaling activity of both beta-catenin and cnxPg. Both exogenous XLEF1 and XTCF3 are sequestered in the cytoplasm of Xenopus cells by cnxPg. Based an these data, we conclude that, in addition to its effects on beta-catenin, cnxPg interacts with other components of the Wnt pathway, perhaps TCFs, and that these interactions contribute to its signaling activity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 22:20:43