“…This model for a stable ternary complex does not contradict the notion that the relative affinities of the subunits change during the cell cycle; indeed, such changes in affinity have been seen in vitro upon CDK phosphorylation of mammalian RB (Zheng et al, 1999;Burke et al, 2010), but altered affinity in vitro does not necessarily imply dissociation in vivo. Our model is consistent with the known association of RBrelated proteins with dozens of effectors, including chromatin modifying proteins, replication proteins, transcription factors, and others that may change in their temporal associations with RB-related proteins to regulate either cell cycle progression or differentiation (Williams and Grafi, 2000;Morris and Dyson, 2001;Egelkrout et al, 2002;Shen, 2002;Ausín et al, 2004;Mosquna et al, 2004;Magyar et al, 2005;Ramírez-Parra and Gutierrez, 2007;Burkhart and Sage, 2008;Jullien et al, 2008;van den Heuvel and Dyson, 2008;Chen et al, 2009;. Our findings provide a basis for further investigation of RB-E2F-DP complexes and how a stable ternary complex may be modified as a switch to drive cell cycle progression.…”