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.
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.
Pilkinton
M
M
Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
Sandoval
R
R
Colamonici
O R
OR
D016475:3T3 Cells; D000818:Animals; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D050704:E2F4 Transcription Factor / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D050720:Retinoblastoma-Like Protein p107 / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D050704:E2F4 Transcription Factor; C512498:LIN-9 protein, mouse; C501563:LIN9 protein, human; C064352:MYBL2 protein, human; D009687:Nuclear Proteins; D020598:Proto-Oncogene Proteins c-myb; D050720:Retinoblastoma-Like Protein p107; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D020169:Caspases; C438246:STRICA protein, Drosophila