Mammalian Mip/LIN-9 interacts with either the p107, p130/E2F4 repressor complex or B-Myb in a cell cycle-phase-dependent context distinct from the Drosophila dREAM complex

Oncogene. 2007 Nov 29;26(54):7535-43. doi: 10.1038/sj.onc.1210562. Epub 2007 Jun 11.


Mammalian Mip/LIN-9 is a cell cycle regulatory protein that is negatively regulated by CDK4/cyclin D. It has been demonstrated that Mip/LIN-9 collaborates with B-Myb during S and G(2)/M in the induction of cyclins A and B, and CDK1. The ortholog of Mip/LIN-9 in Drosophila, Mip130, is part of a large multisubunit protein complex that includes RBF, repressor E2Fs and Myb, in what was termed the dREAM complex. A similar complex, although lacking B-Myb, was also described in Caenorhabditis elegans. Here, we demonstrate that unlike Drosophila, Mip/LIN-9 has mutually exclusive and cell cycle-phase-specific interactions with the mammalian orthologs of the dREAM complex. In G(0)/early G(1), Mip/LIN-9 forms a complex with E2F4 and p107 or p130, while in late G(1)/S phase, it associates with B-Myb. The separation of Mip/LIN-9 from p107,p130/E2F4 is likely driven by phosphorylation of the pocket proteins by CDK4 since Mip/LIN-9 fails to interact with phosphorylated forms of p107,p130. Importantly, the repressor complex that Mip/LIN-9 forms with p107 takes functional precedence over the transcriptional activation linked to the Mip/LIN-9 and B-Myb interaction since expression of p107 blocks the activation of the cyclin B promoter triggered by B-Myb and Mip/LIN-9.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3T3 Cells
  • Animals
  • Caspases / metabolism*
  • Cell Cycle
  • Cell Cycle Proteins / metabolism*
  • Cell Nucleus / physiology
  • DNA-Binding Proteins / metabolism*
  • Drosophila / metabolism
  • Drosophila Proteins / metabolism*
  • E2F4 Transcription Factor / metabolism*
  • HeLa Cells
  • Humans
  • Mice
  • Nuclear Proteins / metabolism*
  • Proto-Oncogene Proteins c-myb / metabolism*
  • Retinoblastoma-Like Protein p107 / metabolism*
  • Trans-Activators / metabolism*
  • Tumor Suppressor Proteins / metabolism*


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • E2F4 Transcription Factor
  • LIN-9 protein, mouse
  • LIN9 protein, human
  • MYBL2 protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-myb
  • Retinoblastoma-Like Protein p107
  • Trans-Activators
  • Tumor Suppressor Proteins
  • Caspases
  • STRICA protein, Drosophila