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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 volume 26, pages 7535–7543 (2007)Cite this article

Abstract

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 G2/M in the induction of cyclins A and B, and CDK1. The ortholog of Mip/LIN-9 in D rosophila, 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 G0/early G1, Mip/LIN-9 forms a complex with E2F4 and p107 or p130, while in late G1/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.

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Abbreviations

CDK:

cyclin-dependent kinase

dREAM:

D rosophila RB, E2F and Myb complex

IP:

immunoprecipitation

mAb:

monoclonal antibody

Mip:

Myb-interacting protein

pAb:

polyclonal antibody

WB:

western blotting

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Acknowledgements

This work has been supported by The National Institutes of Health Grant GM54709 (ORC). MP was supported by an NIH Institutional T32 training grant, ‘Training Program in Signal Transduction and Cellular Endocrinology’, T32 DK07739 from the National Institute of Diabetes and Digestive and Kidney Disorders.

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  1. M Pilkinton and R Sandoval: These authors contributed equally to this work.

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  1. Department of Pharmacology, University of Illinois, Chicago, IL, USA

    M Pilkinton, R Sandoval & O R Colamonici

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  1. M Pilkinton
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Correspondence to O R Colamonici.

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Pilkinton, M., Sandoval, R. & Colamonici, O. 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 26, 7535–7543 (2007). https://doi.org/10.1038/sj.onc.1210562

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