Model of pRb Function

The experimental data on the function of pRb allow a model to be described that unites the signal elements involved in Gi control in a very logical manner (according to Weinberg, 1995). 

The crucial control element of pRb function is its phosphorylation status, which can be considered as a switch. At the start of Gi phase, pRb exists in an imderphosphorylated form. In this form, it fimctions as a brake on the progress of the cell cycle. The brake is lifted when pRb is phosphorylated by the central components of the cell cycle apparatus. The protein complexes involved in phosphorylation of pRb are CDK4/cyclinD, CDK2/cyclin E and CDK2/cyclin A. 

Overall, pRb is phosphorylated by the activated CDKs at many (ca. 11) Ser/Thr residues. The different CDKs preferentially phosphorylate pRb at distinct sites. There is evidence that the various phosphorylation events have different effects on pRb function. 

Tlie effector function of pRb is its control of the function of transcription factors that belong to the E2F family. pRb binds to proteins of the E2F family and thus controls their transcription-activating function. 

Transcription factor E2F thus controls the expression of proteins that are required for further progress of the cell cycle. Overall, the transcription-controlling activity of E2F can be assigned a central function in progress of Gi phase and also S phase. 

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Fig. 14.7 Model of pRb function in control of cell proliferation and apoptosis.

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