Regulation of cell cycle by Retinoblastoma protein: Systems Biology approach

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Comprehensive Map of Molecular Interactions in RB/E2F Pathway

 
 
 
 

Modules - APC (click here for interactive version)

CDC20 and CDH1 are auxiliary proteins of the APC (Anaphase Promoting Complex) that tags the proteins for ubiquitination.

CDC20 participates in a negative feedback loop involving CycB1/CDC2: when phosphorylated by the CDK complex, CDC20 binds to the APC and only then can it bring the cyclins to the APC for degradation during M phase (Lukas and Bartek, 2004). CDC20 activity is shut off in early G1 whereas CDH1 remains active throughout G1 phase and is inactivated at the G1/S transition. It is at this transition that CycA2/CDC2 and CycB1/CDC2 (Bembenek and Yu, 2001) phosphorylate CDH1 and keep it inactive for a proper DNA synthesis (Lukas et al., 1999). The reverse reaction is controlled by the phosphatase CDC14A activated in late M and until the end of M phase (Fung and Poon, 2005). CDH1 binds to APC in its unphosphorylated form and mediates the degradation of CycA2/CDK2 (Fung and Poon, 2005).

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