Interaction of c-Myc with the pRb-related protein p107 results in inhibition of c-Myc-mediated transactivation

Roderick L. Beijersbergen, E. Marielle Hijmans, Liang Zhu, René Bernards

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

The product of the c-myc proto-oncogene, c-Myc, is a sequence-specific DNA binding protein with an N-terminal transactivation domain and a C-terminal DNA binding domain. Several lines of evidence indicate that c-Myc activity is essential for normal cell cycle progression. Since the abundance of c-Myc during the cell cycle is constant, c-Myc's activity may be regulated at a post-translational level. We have shown previously that the N-terminus of c-Myc can form a specific complex with the product of the retinoblastoma gene, pRb, in vitro. These data suggested a model in which pRb, or pRb-related proteins, regulate c-Myc activity through direct binding. We show here that the pRb-related protein p107, but not pRb itself, forms a specific complex with the N-terminal transactivation domain of c-Myc in vivo. Binding of p107 to c-Myc causes a significant inhibition of c-Myc transactivation. Expression of c-Myc releases cells from a p107-induced growth arrest, but not from pRb-induced growth arrest. Our data suggest that p107 can control c-Myc activity through direct binding to the transactivation domain and that c-Myc is a target for p107-mediated growth suppression.

Original languageEnglish (US)
Pages (from-to)4080-4086
Number of pages7
JournalEMBO Journal
Volume13
Issue number17
StatePublished - 1994
Externally publishedYes

Fingerprint

Transcriptional Activation
Cells
Proto-Oncogene Proteins c-myc
Cell Cycle
Proteins
Growth
DNA-Binding Proteins
Retinoblastoma Genes
myc Genes
Genes
DNA

Keywords

  • c-Myc
  • p107
  • pRb
  • Transactivation

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Interaction of c-Myc with the pRb-related protein p107 results in inhibition of c-Myc-mediated transactivation. / Beijersbergen, Roderick L.; Hijmans, E. Marielle; Zhu, Liang; Bernards, René.

In: EMBO Journal, Vol. 13, No. 17, 1994, p. 4080-4086.

Research output: Contribution to journalArticle

Beijersbergen, RL, Hijmans, EM, Zhu, L & Bernards, R 1994, 'Interaction of c-Myc with the pRb-related protein p107 results in inhibition of c-Myc-mediated transactivation', EMBO Journal, vol. 13, no. 17, pp. 4080-4086.
Beijersbergen, Roderick L. ; Hijmans, E. Marielle ; Zhu, Liang ; Bernards, René. / Interaction of c-Myc with the pRb-related protein p107 results in inhibition of c-Myc-mediated transactivation. In: EMBO Journal. 1994 ; Vol. 13, No. 17. pp. 4080-4086.
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