Transforming growth factor β-induced proliferative arrest mediated by TRIM26- dependent TAF7 degradation and its antagonism by MYC

Tadashi Nakagawa, Masaki Hosogane, Makiko Nakagawa, Akane Morohoshi, Ryo Funayama, Keiko Nakayama

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Recognition of gene promoters by RNA polymerase II is mediated by general transcription factor IID (TFIID), which has been thought to be a static complex and to play a passive role in the regulation of gene expression under the instruction of gene-specific transcription factors. Here we show that transforming growth factor β (TGF-β) induced degradation of the TFIID subunit TAF7 in cultured mouse mammary epithelial cells and that this effect was required for proliferative arrest in response to TGF-β stimulation. TGF-β stimulated transcription of the gene for the ubiquitin ligase TRIM26, which was shown to ubiquitylate TAF7 and thereby to target it for proteasomal degradation. Sustained exposure of cells to TGF-β resulted in recovery from proliferative arrest in association with amplification of the Myc proto-oncogene, with MYC inhibiting TRIM26 induction by TGF-β. Our data thus show that TFIID is not simply a general mediator of transcription but contributes to the regulation of transcription in response to cell stimulation, playing a key role in the cytostatic function of TGF-β.

Original languageEnglish
Article numbere00449-17
JournalMolecular and cellular biology
Volume38
Issue number5
DOIs
Publication statusPublished - 2018 Mar 1

Keywords

  • MYC
  • Proliferation arrest
  • TAF7
  • TGF-β
  • TRIM26
  • Ubiquitylation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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