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

Research output: Contribution to journalArticlepeer-review

13 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

All Science Journal Classification (ASJC) codes

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

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