Cell fate determination factor DACH1 inhibits c-Jun-induced contact-independent growth

Kongming Wu, Manran Liu, Anping Li, Howard Donninger, Mahadev Rao, Xuanmao Jiao, Michael P. Lisanti, Ales Cvekl, Michael Birrer, Richard G. Pestell

Research output: Contribution to journalArticle

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Abstract

The cell fate determination factor DACH1 plays a key role in cellular differentiation in metazoans. DACH1 is engaged in multiple context-dependent complexes that activate or repress transcription. DACH1 can be recruited to DNA via the Six1/Eya bipartite transcription (DNA binding/coactivator) complex. c-Jun is a critical component of the activator protein (AP)-1 transcription factor complex and can promote contact-independent growth. Herein, DACH1 inhibited c-Jun-induced DNA synthesis and cellular proliferation. Excision of c-Jun with Cre recombinase, in c-junf1/f1 3T3 cells, abrogated DACH1-mediated inhibition of DNA synthesis. c-Jun expression rescued DACH1-mediated inhibition of cellular proliferation. DACH1 inhibited induction of c-Jun by physiological stimuli and repressed c-jun target genes (cyclin A, β-PAK, and stathmin). DACH1 bound c-Jun and inhibited AP-1 transcriptional activity, c-jun and c-fos were transcriptionally repressed by DACH1, requiring the conserved N-terminal (dac and ski/sno [DS]) domain. c-fos transcriptional repression by DACH1 requires the SRF site of the c-fos promoter. DACH1 inhibited c-Jun transactivation through the δ domain of c-Jun. DACH1 coprecipitated the histone deacetylase proteins (HDAC1, HDAC2, and NCoR), providing a mechanism by which DACH1 represses c-Jun activity through the conserved δ domain. An oncogenic v-Jun deleted of the δ domain was resistant to DACH1 repression. Collectively, these studies demonstrate a novel mechanism by which DACH1 blocks c-Jun-mediated contact-independent growth through repressing the c-Jun δ domain.

Original languageEnglish (US)
Pages (from-to)755-767
Number of pages13
JournalMolecular Biology of the Cell
Volume18
Issue number3
DOIs
StatePublished - Mar 2007

Fingerprint

DNA
Transcription Factor AP-1
Growth
Stathmin
Histone Deacetylase 1
Cell Proliferation
jun Genes
Cyclin A
3T3 Cells
Transcriptional Activation
Transcription Factors
Proteins
Cre recombinase

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Wu, K., Liu, M., Li, A., Donninger, H., Rao, M., Jiao, X., ... Pestell, R. G. (2007). Cell fate determination factor DACH1 inhibits c-Jun-induced contact-independent growth. Molecular Biology of the Cell, 18(3), 755-767. https://doi.org/10.1091/mbc.E06-09-0793

Cell fate determination factor DACH1 inhibits c-Jun-induced contact-independent growth. / Wu, Kongming; Liu, Manran; Li, Anping; Donninger, Howard; Rao, Mahadev; Jiao, Xuanmao; Lisanti, Michael P.; Cvekl, Ales; Birrer, Michael; Pestell, Richard G.

In: Molecular Biology of the Cell, Vol. 18, No. 3, 03.2007, p. 755-767.

Research output: Contribution to journalArticle

Wu, K, Liu, M, Li, A, Donninger, H, Rao, M, Jiao, X, Lisanti, MP, Cvekl, A, Birrer, M & Pestell, RG 2007, 'Cell fate determination factor DACH1 inhibits c-Jun-induced contact-independent growth', Molecular Biology of the Cell, vol. 18, no. 3, pp. 755-767. https://doi.org/10.1091/mbc.E06-09-0793
Wu, Kongming ; Liu, Manran ; Li, Anping ; Donninger, Howard ; Rao, Mahadev ; Jiao, Xuanmao ; Lisanti, Michael P. ; Cvekl, Ales ; Birrer, Michael ; Pestell, Richard G. / Cell fate determination factor DACH1 inhibits c-Jun-induced contact-independent growth. In: Molecular Biology of the Cell. 2007 ; Vol. 18, No. 3. pp. 755-767.
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