Dr. DeCaprio’s lab identified an 8-protein complex that we termed DREAM based on its similarity to complexes previously identified by genetic and biochemical studies in C. elegans and D. melanogaster. We determined that the mammalian DREAM complex bound specifically to the promoters of all cell cycle regulated, E2F-dependent, genes and repressed their expression during cellular quiescence. We determined that the DYRK1A kinase was required for assembly of the DREAM complex during quiescence. We found that the DREAM complex underwent a metamorphosis during cell cycle progression with the MuvB component being released from p130, E2F4 and DP1 during the G1 phase of the cell cycle and subsequently binding to B-MYB (MYBL2) and FOXM1 to form the MMB-FOXM1 complex that specifically activates expression of several hundred genes required for progression during G2 and M phase. The DeCaprio Lab established the foundation that the DREAM complex serves as a master coordinator of cell cycle gene expression.
  1. Litovchick L, Sadasivam S, Florens L, Zhu X, Swanson SK, Velmurugan S, Chen R, Washburn MP, Liu XS, DeCaprio JA. Evolutionarily Conserved Multisubunit RBL2/p130 and E2F4 Protein Complex Represses Human Cell Cycle-Dependent Genes in Quiescence. Mol Cell. 2007;26(4):539-551. PMID: 17531812
  2. Fischer M, Grossmann P, Padi M, DeCaprio JA. Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks. Nucleic Acids Res. 2016 Jul 27;44(13):6070-86. PMCID: PMC4994865
  3. Schade AE, Oser MG, Nicholson HE, DeCaprio JA. Cyclin D-CDK4 relieves cooperative repression of proliferation and cell cycle gene expression by DREAM and RB. Oncogene. 2019 Jun;38(25):4962-4976. PMCID: PMC6586519
  4. Schade AE, Fischer M, DeCaprio JA. RB, p130 and p107 differentially repress G1/S and G2/M genes after p53 activation. Nucleic Acids Res. 2019 Dec 2;47(21):11197-11208. PMCID: PMC6868438
  5. Branigan TB, Kozono D, Schade AE, Deraska P, Rivas HG, Sambel L, Reavis HD, Shapiro GI, D'Andrea AD, DeCaprio JA. MMB-FOXM1-driven premature mitosis is required for CHK1 inhibitor sensitivity. Cell Rep. 2021 Mar 2;34(9):108808. doi: 10.1016/j.celrep.2021.108808. PMID: 33657372