The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Sox9 Inhibits Wnt Signaling by Promoting β-Catenin Phosphorylation in the Nucleus
Open accessAbstract
Chondrocyte fate determination and maintenance requires Sox9, an intrinsic transcription factor, but is inhibited by Wnt/beta-catenin signaling activated by extrinsic Wnt ligands. Here we explored the underlying molecular mechanism by which Sox9 antagonizes the Wnt/beta-catenin signaling in chondrocyte differentiation. We found that Sox9 employed two distinct mechanisms to inhibit Wnt/beta-catenin signaling: the Sox9 N terminus is necessary and sufficient to promote beta-catenin degradation, whereas the C terminus is required to inhibit beta-catenin transcriptional activity without affecting its stability. Sox9 binds to beta-catenin and components of the beta-catenin "destruction complex," glycogen synthase kinase 3 and beta-transducin repeat containing protein, to promote their nuclear localization. Independent of its DNA binding ability, nuclear localization of Sox9 is both necessary and sufficient to enhance beta-catenin phosphorylation and its subsequent degradation. Thus, one mechanism whereby Sox9 regulates chondrogenesis is to promote efficient beta-catenin phosphorylation in the nucleus. This mechanism may be broadly employed by other intrinsic cell fate determining transcription factors to promptly turn off extrinsic inhibitory Wnt signaling mediated by beta-catenin.
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Akiyama, H., Chaboissier, M.-C., Martin, J. F., Schedl, A., & de Crombrugghe, B. (2002) · Genes & Development · doi:10.1101/gad.1017802 · Cited by 1,721
Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells
Stambolic, V., Ruel, L., & Woodgett, J. R. (1996) · Current Biology · doi:10.1016/s0960-9822(02)70790-2 · Cited by 1,321
Wnt Signaling in Oncogenesis and Embryogenesis--a Look Outside the Nucleus
Peifer, M., & Polakis, P. (2000) · Science · doi:10.1126/science.287.5458.1606 · Cited by 1,253
The transcription factor Sox9 is required for cranial neural crest development in Xenopus
Spokony, R. F., Aoki, Y., Saint-Germain, N., Magner-Fink, E., & Saint-Jeannet, J.-P. (2002) · Development · doi:10.1242/dev.129.2.421 · Cited by 295
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Metadata
- Authors
- Topol, L., Chen, W., Song, H., Day, T. F., & Yang, Y.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 284
- Issue
- 5
- Pages
- 3323-3333
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2140034839
- Cited by
- 230
- References
- 4
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
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