Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade

Yinhua Jin, Teni Anbarchian, Peng Wu, Abby Sarkar, Matt Fish, Weng Chuan Peng, Roel Nusse

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Cell proliferation is tightly controlled by inhibitors that block cell cycle progression until growth signals relieve this inhibition, allowing cells to divide. In several tissues, including the liver, cell proliferation is inhibited at mitosis by the transcriptional repressors E2F7 and E2F8, leading to formation of polyploid cells. Whether growth factors promote mitosis and cell cycle progression by relieving the E2F7/E2F8-mediated inhibition is unknown. We report here on a mechanism of cell division control in the postnatal liver, in which Wnt/β-catenin signaling maintains active hepatocyte cell division through Tbx3, a Wnt target gene. The TBX3 protein directly represses transcription of E2f7 and E2f8, thereby promoting mitosis. This cascade of sequential transcriptional repressors, initiated by Wnt signals, provides a paradigm for exploring how commonly active developmental signals impact cell cycle completion.

Original languageEnglish
Article numbere2203849119
Pages (from-to)e2203849119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number30
DOIs
Publication statusPublished - 26 Jul 2022
Externally publishedYes

Keywords

  • liver
  • proliferation
  • Wnt
  • Animals
  • Mitosis
  • beta Catenin/metabolism
  • T-Box Domain Proteins/metabolism
  • Hepatocytes/cytology
  • Mice
  • Repressor Proteins/genetics
  • Wnt Signaling Pathway

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