Dual functions of DP1 promote biphasic Wnt-on and Wnt-off states during anteroposterior neural patterning

Wan Tae Kim, Hyunjoon Kim, Vladimir L. Katanaev, Seung Joon Lee, Tohru Ishitani, Boksik Cha, Jin Kwan Han, Eek Hoon Jho

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12 Citations (Scopus)

Abstract

DP1, a dimerization partner protein of the transcription factor E2F, is known to inhibit Wnt/β-catenin signalling along with E2F, although the function of DP1 itself was not well characterized. Here, we present a novel dual regulatory mechanism of Wnt/β-catenin signalling by DP1 independent from E2F. DP1 negatively regulates Wnt/β-catenin signalling by inhibiting Dvlĝ€"Axin interaction and by enhancing poly-ubiquitination of 2-catenin. In contrast, DP1 positively modulates the signalling upon Wnt stimulation, via increasing cytosolic β-catenin and antagonizing the kinase activity of NLK. In Xenopus embryos, DP1 exerts both positive and negative roles in Wnt/β-catenin signalling during anteroposterior neural patterning. From subcellular localization analyses, we suggest that the dual roles of DP1 in Wnt/ 2-catenin signalling are endowed by differential nucleocytoplasmic localizations. We propose that these dual functions of DP1 can promote and stabilize biphasic Wnt-on and Wnt-off states in response to a gradual gradient of Wnt/β-catenin signalling to determine differential cell fates.

Original languageEnglish
Pages (from-to)3384-3397
Number of pages14
JournalEMBO Journal
Volume31
Issue number16
DOIs
Publication statusPublished - Aug 15 2012

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Kim, W. T., Kim, H., Katanaev, V. L., Joon Lee, S., Ishitani, T., Cha, B., ... Jho, E. H. (2012). Dual functions of DP1 promote biphasic Wnt-on and Wnt-off states during anteroposterior neural patterning. EMBO Journal, 31(16), 3384-3397. https://doi.org/10.1038/emboj.2012.181